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Alcoholism Research:
2002-2006
Schizophr Bull. 2006 Aug 3; [Epub ahead of print]
Psychotic Spectrum Disorders and Alcohol Abuse: A Review of
Pharmacotherapeutic Strategies and a Report on the Effectiveness of Naltrexone
and Disulfiram.
Petrakis IL, Nich C, Ralevski E.
Department of Psychiatry, Yale University School of Medicine, VA Connecticut
Healthcare System, 950 Campbell Avenue, Mail Code 116A, West Haven, CT 06516.
The rate of substance-use disorders in patients with mental illnesses within the
psychotic spectrum, such as schizophrenia, schizoaffective disorder, and bipolar
disorder, is higher than the rate observed in the general population and is
associated with significant morbidity and mortality. Although there are
currently 3 medications approved by the Food and Drug Administration for the
treatment of alcohol dependence, no medications have been approved for the
specific treatment of dually diagnosed patients. A small but growing body of
literature supports the use of 2 of these medications, disulfiram and naltrexone,
in dually diagnosed individuals. This article outlines a review of the
literature about the use of disulfiram and naltrexone for alcoholism and in
patients with comorbid mental illness. In addition, results are presented of a
12-week randomized clinical trial of disulfiram and naltrexone alone and in
combination for individuals with Axis I disorders and alcohol dependence who
were also receiving intensive psychosocial treatment. Individuals with a
psychotic spectrum disorder, including schizophrenia, schizoaffective disorder,
and bipolar disorder, had worse alcohol outcomes than those without a psychotic
spectrum disorder. Individuals with a psychotic spectrum disorder had better
alcohol-use outcomes on an active medication compared with placebo, but there
was no clear advantage of disulfiram or naltrexone or of the combination.
Retention rates and medication compliance in the study were high and exceeded
80%. Pharmacotherapeutic strategies should take into account the advantages and
disadvantages of each medication. Future directions of pharmacotherapeutic
options are also discussed.
-----
Addict Behav. 2006 Jul 28; [Epub ahead of print]
A campus-based motivational enhancement group intervention
reduces problematic drinking in freshmen male college students.
Labrie JW, Pedersen ER, Lamb TF, Quinlan T.
Loyola Marymount University, Department of Psychology, 1 LMU Drive, Los Angeles,
CA 90045, United States.
The current study employs an adaptation to Motivational Interviewing (AMI) group
intervention with freshmen male undergraduates. The program follows suggestions
of the National Institute on Alcohol Abuse and Alcoholism for effective
interventions with problematic college student drinking, and combines several
empirically validated strategies to prevent drinking problems throughout
college. All participants reduced drinking and alcohol-related problems; heavier
drinkers and those experiencing the most alcohol-related problems reduced
drinking most. Additionally, freshmen who completed the intervention were less
likely than their non-intervention freshmen male peers to commit alcohol-related
violations of campus policies. In addition to the reductions in problematic
drinking, the group AMI has advantages over individual formats because larger
numbers of students can benefit with comparable expenditures of time and effort.
-----
Cleve Clin J Med. 2006 Jul;73(7):641-4, 647-8, 650-1, passim.
Drug adjuncts for treating alcohol dependence.
Collins GB, McAllister MS, Adury K.
Section head, Alcohol and Drug Recovery Center, Department of Psychiatry and
Psychology, Cleveland Clinic, Cleveland Clinic Foundation, OH 44195, USA.
colling@ccf.org
Three drugs are approved by the US Food and Drug Administration for treating
alcoholism: disulfiram, naltrexone, and acamprosate. Drugs approved for other
indications that are being used experimentally or "off-label" include nalmafene,
topiramate, and ondansetron. As we learn more about the pathophysiologic basis
of alcoholism, it is hoped that novel drugs can be developed to help people with
alcohol dependence achieve abstinence, and as a result, curb alcohol-related
morbidity.
-----
Drugs. 2006;66(9):1229-37.
Pharmacotherapy of alcoholism in patients with co-morbid
psychiatric disorders.
Goldstein BI, Diamantouros A, Schaffer A, Naranjo CA.
Department of Psychiatry, Sunnybrook and Women's College Health Sciences Centre,
University of Toronto, Toronto, Canada.
There has been an exponential increase in recent years of literature pertaining
to the treatment of individuals with alcohol use disorders and co-morbid
psychiatric disorders. Patients with mood and anxiety disorders in particular
have a very high prevalence of alcoholism. Alcoholism confers significant morbid
risks to patients with psychiatric disorders, and vice versa, including markedly
increased risk of suicide. Only recently have studies examined the impact of
various psychiatric medications on alcohol use among patients with these
disorders. Evidence supporting the benefits of antidepressants for co-morbid
alcoholism and depression continues to mount. Although these studies have
demonstrated benefits in terms of quantitative decreases in the volume and
frequency of consumption, the benefits in terms of remission from alcoholism
have yet to be shown conclusively. The first randomised, controlled trial
involving subjects with co-morbid alcoholism and bipolar disorder was recently
conducted, yielding promising results for valproate in this population. The
literature regarding co-morbid alcoholism and anxiety disorders has also seen
recent progress, particularly in the study of post-traumatic stress disorder (PTSD).
A placebo-controlled study of sertraline suggests some benefit in terms of
alcohol use among individuals with early-onset PTSD and less severe alcohol
dependence. Atypical antipsychotics such as olanzapine and quetipaine have been
examined in several open studies of subjects with alcoholism co-morbid with a
variety of psychiatric conditions including bipolar disorder, PTSD and
schizophrenia. This paper selectively reviews the evidence that is currently
available for the pharmacological management of alcoholism among persons with
co-morbid psychiatric illness. Effectiveness, safety and tolerability are
considered, and directions for future study are discussed.
-----
Alcohol Res Health. 2006;29(1):36-40.
Computer-based tools for diagnosis and treatment of alcohol
problems.
Hester RK, Miller JH.
Research Division, Behavior Therapy Associates, LLP, Albuquerque, NM, USA.
Diagnosis and treatment of alcohol-related problems are time-intensive
procedures that often are difficult to implement in busy clinical settings.
Computer-based tools are one approach that may enhance the availability and
cost-effectiveness of assessment and intervention and also may offer other
advantages over face-to-face interventions. Several PC- and Internet-based
programs have been developed that can be used for assessing alcohol problems,
some of which are based on existing screening instruments. Other programs have
demonstrated effectiveness as interventions, serving to increase patient
motivation and reduce alcohol-associated harm through skill building.
Investigators also have begun to analyze the mechanisms through which
computer-based programs can induce these effects. Future efforts should be aimed
at developing and evaluating additional computer-based interventions,
particularly for specific patient subgroups, and at removing barriers to the
incorporation of such programs into clinical practice.
-----
Presse Med. 2006 May;35(5 Pt 2):831-9.
["Drinking less is better". Combining early identification and
brief intervention for patients at risk]
[Article in French]
Michaud P, Dewost AV, Fouilland P.
Programme Boire moins c'est mieux, ANPAA, Nanterre (92). bmcm@anpa.asso.fr
Above 210 grams a week in men and 140 grams a week in women, alcohol consumption
is a risk factor for avoidable mortality in the general population. Beyond
specific risk situations (for example, pregnancy, medication that interferes
with alcohol, operating machinery, or a history of alcohol-dependence) in which
abstinence is recommended, consumption of levels below these thresholds (which
represent respectively an average of 3 and 2 drinks a day) involves little risk.
Above these thresholds, the frequency of secondary disease (principally cancers
and cardiovascular, neurologic, hepatologic, and gastroenterologic disorders)
contributes to reducing life expectancy in drinkers. Early identification of
excessive but not dependent alcohol consumption is the only means of avoiding
the morbidity and mortality associated with drinking. Health providers too often
confound alcoholism with alcohol-related problems. Half of the deaths associated
with alcohol, however, concern people who are not dependent on it. Excessive
drinkers must be identified early if they are to be counseled and helped to
reduce their consumption. The brief intervention is a counseling practice easy
to learn. When practiced wisely (in people who drink to excess but are not
alcohol-dependent), this brief intervention takes 10 minutes and provides
information, motivational and behavioral counseling. It can be learned in two
evenings and is immediately transposable into daily practice. The brief
intervention is effective. It leads to a reduction in consumption below the risk
thresholds in 10-50% of cases. Any trained care giver in primary care, hospital,
or preventive medicine can provide it. Tools for identification and intervention
are available. Two screening questionnaires have been validated in French, the
AUDIT (a self-administered questionnaire) and the FACE (a questionnaire
completed by the doctor). The procedures and philosophy of interventions are
defined and validated, and training is available for all providers who want to
acquire this practice. This original research activity leads to a new public
health effort. WHO, the national association for prevention of alcoholism and
addiction, and various public health agencies have developed the experimental
program 'Drinking less is better', intended to adapt WHO tools for early
identification and brief intervention (EIBI) to French medical practice. This
research-activity was conducted in close association with its targets
(especially general practitioners) and has contributed to defining the
conditions for the diffusion of this EIBI in France. Based on its conclusions,
the health authorities have launched a national training strategy.
-----
JAMA. 2006 May 3;295(17):2003-17. Comment in: JAMA. 2006 May 3;295(17):2075-6.
Combined pharmacotherapies and behavioral interventions for
alcohol dependence: the COMBINE study: a randomized controlled trial.
Anton RF, O'Malley SS, Ciraulo DA, Cisler RA, Couper D, Donovan DM, Gastfriend
DR, Hosking JD, Johnson BA, LoCastro JS, Longabaugh R, Mason BJ, Mattson ME,
Miller WR, Pettinati HM, Randall CL, Swift R, Weiss RD, Williams LD, Zweben A;
COMBINE Study Research Group.
Center for Drug and Alcohol Programs, Medical University of South Carolina,
Charleston 29425, USA. antonr@musc.edu
CONTEXT: Alcohol dependence treatment may include medications, behavioral
therapies, or both. It is unknown how combining these treatments may impact
their effectiveness, especially in the context of primary care and other
nonspecialty settings. OBJECTIVES: To evaluate the efficacy of medication,
behavioral therapies, and their combinations for treatment of alcohol dependence
and to evaluate placebo effect on overall outcome. DESIGN, SETTING, AND
PARTICIPANTS: Randomized controlled trial conducted January 2001-January 2004
among 1383 recently alcohol-abstinent volunteers (median age, 44 years) from 11
US academic sites with Diagnostic and Statistical Manual of Mental Disorders,
Fourth Edition, diagnoses of primary alcohol dependence. INTERVENTIONS: Eight
groups of patients received medical management with 16 weeks of naltrexone (100
mg/d) or acamprosate (3 g/d), both, and/or both placebos, with or without a
combined behavioral intervention (CBI). A ninth group received CBI only (no
pills). Patients were also evaluated for up to 1 year after treatment. MAIN
OUTCOME MEASURES: Percent days abstinent from alcohol and time to first heavy
drinking day. RESULTS: All groups showed substantial reduction in drinking.
During treatment, patients receiving naltrexone plus medical management (n =
302), CBI plus medical management and placebos (n = 305), or both naltrexone and
CBI plus medical management (n = 309) had higher percent days abstinent (80.6,
79.2, and 77.1, respectively) than the 75.1 in those receiving placebos and
medical management only (n = 305), a significant naltrexone x behavioral
intervention interaction (P = .009). Naltrexone also reduced risk of a heavy
drinking day (hazard ratio, 0.72; 97.5% CI, 0.53-0.98; P = .02) over time, most
evident in those receiving medical management but not CBI. Acamprosate showed no
significant effect on drinking vs placebo, either by itself or with any
combination of naltrexone, CBI, or both. During treatment, those receiving CBI
without pills or medical management (n = 157) had lower percent days abstinent
(66.6) than those receiving placebo plus medical management alone (n = 153) or
placebo plus medical management and CBI (n = 156) (73.8 and 79.8, respectively;
P<.001). One year after treatment, these between-group effects were similar but
no longer significant. CONCLUSIONS: Patients receiving medical management with
naltrexone, CBI, or both fared better on drinking outcomes, whereas acamprosate
showed no evidence of efficacy, with or without CBI. No combination produced
better efficacy than naltrexone or CBI alone in the presence of medical
management. Placebo pills and meeting with a health care professional had a
positive effect above that of CBI during treatment. Naltrexone with medical
management could be delivered in health care settings, thus serving
alcohol-dependent patients who might otherwise not receive treatment. TRIAL
REGISTRATION: clinicaltrials.gov Identifier: NCT00006206.
-----
J Am Coll Health. 2006 Mar-Apr;54(5):301-4.
HEADS UP! A nested intervention with freshmen male college
students and the broader campus community to promote responsible drinking.
LaBrie JW, Pedersen ER, Lamb TF, Bove L.
Department of Psychology, Loyola Marymount University, Los Angeles, CA 90045,
USA. jlabrie@lmu.edu
The National Institute on Alcohol Abuse and Alcoholism developed several
guidelines for effective interventions in dealing with problematic college
student drinking, including targeted individual interventions paired with
broader campus community involvement. The project Heads UP! combines these
suggestions in an effort to intervene with high-risk first-year male college
students. The objective of the program is to reduce campus alcohol-related
negative events and prevent these high-risk students from developing dangerous
drinking patterns throughout college. The project provides an environment that
supports students in actively following the goals outlined by the intervention,
and it actively impacts the overall campus by helping students make responsible
drinking decisions. Promising results are forthcoming, and the authors encourage
other universities to design and adopt similar campus-supported programs nested
within the broader campus community that target high-risk populations on campus.
-----
Pharmacol Ther. 2006 Mar 15; [Epub ahead of print]
Pharmacological treatment of alcohol dependence: Target symptoms
and target mechanisms.
Heilig M, Egli M.
NIAAA 10 Center Drive, 10/1E-5334 Bethesda, MD 20892-1610, United States.
Alcoholism is a major public health problem and resembles, in many ways, other
chronic relapsing medical conditions. At least 2 separate dimensions of its
symptomatology offer targetable pathophysiological mechanisms. Systems that
mediate positive reinforcement by alcohol are likely important targets in early
stages of the disease, particularly in genetically susceptible individuals. In
contrast, long term neuroadaptive changes caused by chronic alcohol use
primarily appear to affect systems mediating negative affective states, and gain
importance following a prolonged history of dependence. Feasibility of
pharmacological treatment in alcoholism has been demonstrated by a first wave of
drugs which consists of 3 currently approved medications, the aldehyde
dehydrogenase blocker disulfiram, the opioid antagonist naltrexone (NTX) and the
functional glutamate antagonist acamprosate (ACM). The treatment toolkit is
likely to be expanded in the near future. This will improve overall efficacy and
allow individualized treatment, ultimately taking in account the patient's
genetic makeup. In a second wave, early human efficacy data are available for
the 5HT3 antagonist ondansetron, the GABA-B agonist baclofen and the
anticonvulsant topiramate. The third wave is comprised of compounds predicted to
be effective based on a battery of animal models. Using such models, a short
list of additional targets has accumulated sufficient preclinical validation to
merit clinical development. These include the cannabinoid CB1 receptor,
receptors modulating glutamatergic transmission (mGluR2, 3 and 5), and receptors
for stress-related neuropeptides corticotropin releasing factor (CRF),
neuropeptide Y (NPY) and nociceptin. Once novel treatments are developed, the
field faces a major challenge to assure their delivery to patients.
-----
Ann Pharmacother. 2006 Mar;40(3):441-8. Epub 2006 Feb 28.
Valproic Acid management of acute alcohol withdrawal.
Lum E, Gorman SK, Slavik RS.
Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver,
British Columbia, Canada.
OBJECTIVE: To review the clinical evidence to determine the efficacy and safety
of valproic acid in the management of alcohol withdrawal syndrome (AWS). DATA
SOURCES: MEDLINE (1966-February 2006), EMBASE (1980-February 2006), and PubMed
(1966-February 2006) searches identified pertinent studies that were conducted
in humans and published in English. Key words used for identification of
articles included valproic acid, ethanol, alcohol, alcoholism, alcohol
withdrawal delirium, alcohol withdrawal seizures, and substance withdrawal
syndrome. References of identified articles were manually searched. STUDY
SELECTION AND DATA EXTRACTION: All controlled clinical trials that evaluated the
use of valproic acid for the management of AWS in humans were included. DATA
SYNTHESIS: Comparisons were made among various regimens of valproic acid and
traditional therapy with benzodiazepine or nonbenzodiazepine agents. Only 2 of 6
trials reported a statistically significant difference in favor of valproic acid
on endpoints of AWS. However, these differences were of marginal clinical
significance. The number of patients included in these studies did not allow for
adequate evaluation of safety. CONCLUSIONS: The existing limited efficacy and
safety data suggest that valproic acid should not replace conventional therapy
or be used as adjunct therapy for management of mild-to-moderate AWS.
-----
J Consult Clin Psychol. 2006 Feb;74(1):191-8.
Does individual treatment for alcoholic fathers benefit their
children? A longitudinal assessment.
Andreas JB, O'farrell TJ, Fals-Stewart W.
Department of PsychiatryHarvard Medical School, MA, US. jba@hms.harvard.edu.
Psychosocial adjustment in children of alcoholics (COAs; N = 125) was examined
before and at 3 follow-ups in the 15 months after their fathers entered
alcoholism treatment. Before their fathers' treatment, COAs exhibited greater
overall and clinical-level symptomatology than children from the demographically
matched comparison sample, but they improved significantly following their
fathers' treatment. Children of stably remitted fathers were similar to their
demographic counterparts from the comparison sample and had fewer adjustment
problems than children of relapsed fathers, even after accounting for children's
baseline adjustment. Thus, COAs' adjustment improved when their fathers received
treatment for alcoholism, and fathers' recovery from alcoholism was associated
with clinically significant reductions in child problems. ((c) 2006 APA, all
rights reserved).
-----
Dig Dis. 2005;23(3-4):304-9.
Therapy and supportive care of alcoholics: guidelines for
practitioners.
Kienast T, Heinz A.
Department of Psychiatry, Charite, University Medical Center, Campus Mitte,
Berlin, Germany. thorsten.kienast@charite.de
BACKGROUND/AIMS: Alcoholism is a widespread disorder in our societies. However,
only a small percentage of alcoholics appear in specific psychotherapeutic
treatment programs. The vast majority are seen by general practitioners or
experts of other medical specialties where they are treated intensively for
their alcohol-induced comorbidities. But the reason for these comorbidities,
alcoholism itself, is rarely treated. This article provides a guideline for
specialists and non-specialists on how to treat these patients correctly in
nonspecific treatment programs and how to increase motivation to stay abstinent.
Moreover, the concept can be quickly and easily integrated into the daily
routine of any therapeutic team. METHODS: Literature on the therapeutic methods
of brief interventions, motivational interviewing as well as pharmacological
relapse prevention was reviewed in PubMed for the years 1991-2005.
RESULTS/CONCLUSION: The burden of disease of alcoholism and alcohol abuse as
primary disorders is highly evident but often underestimated even by therapists
of various medical disciplines. Systematic studies of the brief intervention
method, motivational interviewing and also pharmacological treatment with
acamprosate have shown that these are potent methods that are easily used to
increase the duration of abstinence and patients' motivation to take part in
further specific treatment. Copyright 2005 S. Karger AG, Basel.
-----
Pharmacopsychiatry. 2006 Jan;39(1):30-4.
Efficacy and safety of outpatient alcohol detoxification with a
combination of tiapride/carbamazepine: additional evidence.
Soyka M, Schmidt F, Schmidt P.
Psychiatric Hospital, University of Munich, Nussbaumstr. 7, 80336 Munich,
Germany. michael.soyka@med.uni-muenchen.de
BACKGROUND: Few medications have been tested for outpatient alcohol
detoxification. Previously we had shown a combination of carbamazepine and
tiapride to be effective in an open study. This database is an extension of our
previous work. METHODS: This was an open prospective study to examine the
efficacy, practicability and medical safety of a combination of tiapride and
carbamazepine in outpatient detoxification of alcohol dependent patients.
Patients were carefully screened for relevant neuropsychiatric disorders and
then seen on a daily outpatient basis. RESULTS: A total number of 116
consecutively admitted patients entered the programme; 107 (92%) successfully
ended the treatment. The mean initial dose for tiapride was 289 mg and for
carbamazepine 502 mg. No serious medical complications or adverse events were
observed except for one case of delirium tremens. Only four patients dropped out
because of side effects. In general medication was well tolerated. Withdrawal
symptomatology as indicated by CIWA-A-scores decreased over time. CONCLUSIONS:
Results from this study give further evidence for a combination of tiapride and
the anticonvulsant carbamazepine as an effective and safe treatment for
outpatient alcohol detoxification in patients with moderate severity of
withdrawal syndrome. Further randomized trials are warranted to examine the
efficacy of this combination in outpatient alcohol withdrawal.
-----
Fortschr Neurol Psychiatr. 2006 Jan;74(1):19-31.
[The effectiveness of psychosocial treatment approaches for
alcohol dependence--a review]
[Article in German]
Bottlender M, Kohler J, Soyka M.
Psychiatrische Klinik und Poliklinik Ludwig-Maximilians-Universitat Munchen,
Munich. MBottlender@aol.com
Treatment approaches which are used in the context of inpatient alcoholism
treatment are frequently neither theoretically justified nor empirically
examined. In view of the enormous method variety the necessity exists for the
development of treatment guidelines in order to offer indicators of promising
treatment achievement for practitioners and pension funds. In a first step, it
must be examined which treatments are effective, which are ineffective and which
are possibly even counter-productive. This article aims to give a comprehensive
review of randomized-controlled studies/meta-analysis on the efficacy of
different treatment approaches. This article reporting the literature review is
part of a larger programme to develop clinical practice guidelines for
rehabilitation which is supported in form, content and finance by the German
Pension Institute for Salaried Employees (Bundesversicherungsanstalt fur
Angestellte, BfA). Summing up, treatment is effective compared to no treatment.
Cognitive behavioural therapy included in a multimodal treatment program is
effective. There are a number of treatment protocols for which controlled
research has consistently found positive results like social skills training,
community reinforcement approaches, behaviour contracting, motivation-enhancing
treatment, and family/marital therapy. There is also a number of commonly used
treatment approaches that brought neither a positive result or were counter
productive like relapse prevention, non-behavioural marital therapy, and insight
psychotherapy, confrontational counseling, education, relaxation training, and
milieu therapy. Support for matching to a specific treatment is weak, but
interventions against alcohol problems should be differentiated according to the
severity of the alcohol problem. Since treatment evaluation is mainly
accomplished in the US and supplying structures with respect to the US and
Germany are substantially different, a generalized transmission of US-American
research results on Germany is to be evaluated carefully. Randomized-controlled
studies are needed in Germany.
-----
BMJ. 2005 Sep 10;331(7516):541.
Effectiveness of treatment for alcohol problems: findings of the
randomised UK alcohol treatment trial (UKATT).
UKATT Research Team.
OBJECTIVE: To compare the effectiveness of social behaviour and network therapy,
a new treatment for alcohol problems, with that of the proved motivational
enhancement therapy. DESIGN: Pragmatic randomised trial. SETTING: Seven
treatment sites around Birmingham, Cardiff, and Leeds. PARTICIPANTS: 742 clients
with alcohol problems; 689 (93.0%) were interviewed at three months and 617
(83.2%) at 12 months. INTERVENTIONS: Social behaviour and network therapy and
motivational enhancement therapy. MAIN OUTCOME MEASURES: Changes in alcohol
consumption, alcohol dependence, and alcohol related problems over 12 months.
RESULTS: Both groups reported substantial reductions in alcohol consumption,
dependence, and problems, and better mental health related quality of life over
12 months. Between groups we found only one significant difference in outcome,
probably due to chance: the social network group showed significantly better
physical health at three months. Non-significant differences at 12 months in the
motivational group relative to the social network group included: the number of
drinks consumed per drinking day had decreased by an extra 1.1 (95% confidence
interval -1.0 to 3.2); scores on the Leeds dependence questionnaire had improved
by an extra 0.6 (-0.7 to 2.0); scores on the alcohol problems questionnaire had
improved by an extra 0.5 (-0.4 to 1.4); but the number of days abstinent from
drinking had increased by 1.2% less (-4.5% to 6.9%). CONCLUSION: The novel
social behaviour and network therapy for alcohol problems did not differ
significantly in effectiveness from the proved motivational enhancement therapy.
-----
Fortschr Neurol Psychiatr. 2005 Sep;73(9):517-25.
[Psychosocial stress and alcohol consumption: interrelations,
consequences and interventions.]
[Article in German]
Walter M, Dammann G, Wiesbeck GA, Klapp BF.
Universitare Psychiatrische Kliniken Basel, Schweiz. marc.walter@upkbs.ch.
BACKGROUND: Psychosocial stress can not only be considered as a result of
chronic alcohol abuse, but also as a cause of high alcohol consumption and it
maintains as a distress syndrome the subsequent course of the alcohol use
disorder. METHODS: This review summarises empirical research results concerning
the interrelations between psychosocial stress and alcohol consumption. The
effects of psychosocial stress are regarded as an ideal-typical process leading
to an increased alcohol intake and later to chronic alcohol abuse, often ending
in alcohol dependence. The aim of the study is to demonstrate the relevance of
stress and distress for diagnostics and therapy of alcohol- related disorders.
RESULTS: At the starting point of high alcohol consumption psychological relief
due to the stress-reducing effects of alcohol is often assumed. A vicious circle
begins, perpetuating psychosocial distress and reinforcing the anxious or
depressive symptoms related to emerging distress syndromes. Associated frequent
comorbidities during the progression are other substance- related disorders,
anxiety and affective disorders. Following alcohol dependence severe somatic and
psychosocial consequences have to be anticipated. CONCLUSIONS: Psychosocial
stress, distress and psychological effects can be understood as an important
psychopathological developmental process of prolonged alcoholism. Symptoms of
distress may be a first relevant evidence of high and hazardous alcohol
consumption. Alcoholic patients should be motivated early to attend psychiatric
and psychotherapeutic treatments to improve their chances for a positive
development. Positive results can be achieved with stress management programs in
alcohol dependent patients. These interventions appear to have comparable
effects to other treatments.
-----
Am J Psychiatry. 2005 Aug;162(8):1423-31.
Anticraving medications for relapse prevention: a possible new
class of psychoactive medications.
O'Brien CP.
University of Pennsylvania/Philadelphia VA Medical Center, Philadelphia, PA
19104-6178, USA. obrien@mail.trc.upenn.edu
Psychiatrists have gradually developed a list of medications that are effective
in the treatment of addictive disorders. Although alcoholism has received the
most attention, nicotine, heroin, and cocaine have all been shown to be
influenced by heredity. Of course, the immediate goal is the reduction of drug
craving and the prevention of relapse to compulsive drug taking. A medication
that can aid in the maintenance of the opiate-free state is naltrexone, a
specific opiate antagonist. Naltrexone is also a good example of an anticraving
medication used in the treatment of alcoholism. Clinicians currently have two
types of medication to aid in the treatment of tobacco use disorder, arguably
the most important addiction. Bupropion and nicotine replacement can be given in
a coordinated fashion to provide the best available results. At present, no
medication is approved by the Food and Drug Administration for the indication of
cocaine addiction. Recently, however, five different medications, already
approved for other purposes, have been found to be effective among cocaine
addicts. Despite clinical trials that show benefit, anticraving medications are
not well known and are underused by clinicians. Addiction is a heterogeneous
condition, with variability in reactivity to the drug of abuse and to the
medications available to treat it. Recent developments in pharmacogenetics may
result in improved selection of medications based on genotype.
-----
Alcohol Clin Exp Res. 2005 Aug;29(8):1432-43.
Follow-up study of anxiety disorder and alcohol dependence in
comorbid alcoholism treatment patients.
Kushner MG, Abrams K, Thuras P, Hanson KL, Brekke M, Sletten S.
Department of Psychiatry, Fairview Riverside Hospital, University of Minnesota,
Minneapolis 55454, USA. kushn001@umn.edu
BACKGROUND: Anxiety disorders are present in a high percentage of alcoholism
treatment patients. We tested the prediction that having a comorbid anxiety
disorder increases the prospective risk for relapse to drinking after alcoholism
treatment. We also explored the prospective associations of specific anxiety
syndromes (and depression) with drinking and anxiety outcomes. METHODS: We
assessed the diagnostic status and daily drinking patterns of 82 individuals
approximately one week after they entered alcoholism treatment (baseline) and
again approximately 120 days later (follow-up) (n=53). RESULTS: Consistent with
study predictions, those with a baseline anxiety disorder (approximately 55%)
were significantly more likely than others to meet various definitions of
drinking relapse over the course of the follow-up. Regression models showed that
baseline social phobia was the single best predictor of a return to any drinking
after treatment, whereas panic disorder was the single best predictor of a
relapse to alcohol dependence after treatment. Having multiple anxiety disorders
(versus any specific anxiety disorder) at the baseline was the strongest
predictor of having at least one active ("persistent") anxiety disorder at the
follow-up. Cross-sectional analysis at the follow-up showed that anxiety
disorder persisted in the absence of a relapse to alcohol dependence far more
often than relapse to alcohol dependence occurred in the absence of a persistent
anxiety disorder. CONCLUSIONS: Screening for comorbid anxiety disorder in
alcoholism treatment patients is warranted and, where found, should be
considered a marker of high relapse risk relative to that of noncomorbid
patients. The capacity of specific anxiety treatment to mitigate relapse risk
among comorbid patients remains an open question.
-----
Arch Intern Med. 2005 Jul 25;165(14):1600-5.
Use of oral topiramate to promote smoking abstinence among
alcohol-dependent smokers: a randomized controlled trial.
Johnson BA, Ait-Daoud N, Akhtar FZ, Javors MA.
Department of Psychiatric Medicine, University of Virginia, Charlottesville
22908-0623, USA. bankolejohnson@virginia.edu
BACKGROUND: Previously, our group has shown that topiramate, a sulfamate-substituted
fructopyranose derivative, is an effective treatment for alcohol dependence.
Herein, we extend that proof-of-concept study by determining whether
cigarette-smoking, alcohol-dependent individuals from the earlier study also
experienced improved smoking outcomes. METHODS: As a subgroup analysis of a
larger double-blind, randomized, controlled, 12-week study comparing topiramate
vs placebo as treatment for alcohol dependence, a 12-week clinical trial
compared topiramate vs placebo in 94 cigarette-smoking, alcohol-dependent
individuals. Of these, 45 were assigned to receive topiramate (escalating dose
from 25 to 300 mg/d) and the remaining 49 had placebo as an adjunct to weekly
standardized medication compliance management. The primary outcome was smoking
cessation ascertained by self-report and confirmed by the level of serum
cotinine (nicotine's major metabolite). RESULTS: Topiramate recipients were
significantly more likely than placebo recipients to abstain from smoking (odds
ratio, 4.46; 95% confidence interval, 1.08-18.39; P = .04). Using a serum
cotinine level of 28 ng/mL or lower to segregate nonsmokers from smokers, we
found that the topiramate group had 4.97 times the odds of being nonsmokers (95%
confidence interval, 1.1-23.4;P = .04). Smoking cessation rates for topiramate
recipients were 19.4% and 16.7% at weeks 9 and 12, respectively, compared with
6.9% at both time points for placebo recipients. CONCLUSION: In this trial,
topiramate (up to 300 mg/d) showed potential as a safe and promising medication
for the treatment of cigarette smoking in alcohol-dependent individuals.
-----
Clin Ther. 2005 Jun;27(6):695-714.
Acamprosate for the treatment of alcohol dependence.
Boothby LA, Doering PL.
Harrison School of Pharmacy, Auburn University, Alabama, USA. lisa.boothby@crhs.net
BACKGROUND: Both inpatient and outpatient treatment centers that focus solely on
psychosocial therapies for the treatment of alcohol dependence have high relapse
rates. Thus, extensive research has focused on the development of pharmacologic
moieties to attenuate the craving for alcohol after acute alcohol
detoxification. Three drug therapies are currently approved by the US Food and
Drug Administration (FDA) for this purpose: disulfiram, naltrexone, and
acamprosate. The latter was approved by the FDA in 2004. OBJECTIVE: This article
describes the pharmacologic properties and clinical usefulness of acamprosate
for the treatment of alcohol dependence. METHODS: Relevant information was
identified through searches of MEDLINE (1966 to March 2005), International
Pharmaceutical Abstracts (1970-2005), Current Contents (1996-2005), and
Cumulative Index to Nursing and Allied Health Literature (1982-Week 2, 2004)
using the key words acamprosate, alcohol dependence, and alcoholism (MeSH).
RESULTS: Acamprosate limited to randomized, controlled clinical trials yielded
33 hits in MEDLINE. Twenty-two articles were reviewed for efficacy end points,
and 10 were reviewed for pharmacology and pharmacokinetics data. Acamprosate
plus pharmacokinetics and pharmacodynamics yielded 19 hits, some of which were
duplicates from the previously described search. Acamprosate plus meta-analysis
(MeSH) yielded 5 hits, naltrexone plus meta-analysis (MeSH) yielded 9 hits, and
disulfiram plus meta-analysis yielded 3 hits. The most recent review articles
and their reference lists were assessed to ensure completeness of literature
searches. Based on these searches, acamprosate is known to be an analogue of
taurine and gamma-aminobutyric acid (GABA), 2 central nervous system
neuromodulators. Acamprosate is thought to share some of the cellular actions of
taurine affecting GABA and glutaminergic receptors in the nucleus accumbens, a
brain region that may be responsible for the reinforcing effects received after
alcohol consumption. Acamprosate is thought to also suppress excitation-induced
calcium entry that results from chronic alcohol exposure, thereby altering the
conformation of the N-methyl-d-aspartate receptors. The percentage of patients
taking acamprosate who were completely abstinent throughout the different
durations of the studies varied from approximately 18% to 61%, compared with 4%
to 45% with placebo. Diarrhea was the most common adverse effect accompanying
acamprosate therapy, and this was generally described as dose related and
transient. CONCLUSIONS: Acamprosate is associated with modest treatment effects.
Its efficacy is similar to naltrexone, and the combination of acamprosate and
naltrexone appears to be more efficacious than acamprosate alone, when combined
with psychosocial interventions.
-----
Rev Med Suisse. 2005 Jun 29;1(26):1728-30, 1732-3.
[Does disulfiram still have a role in alcoholism treatment?]
[Article in French]
Blanc M, Daeppen JB.
CTA-MP16, CHUV, 1011 Lausanne.
What is the place of disulfiram in the treatment of alcohol dependence since
anti-craving pharmacological molecules (acamprosate, naltrexone) were launched
on the market? Considering methodological limitations, available studies do not
allow to conclude about disulfiram's efficacy. Clinical observations indicate
however that disulfiram should keep a place in the treatment of
alcohol-dependence considering favourable outcome for some patients. Disulfiram
implants have however to be avoided. Side effects and possible adverse reactions
should not be a barrier to its use. Disulfiram shouldn't be given during
pregnancy and to patients with instable cardio-vascular disease. Its
prescription justifies a close monitoring of liver tests for patients with
abnormal hepatic function.
-----
Eur Addict Res. 2005;11(4):197-203.
A randomised clinical trial of in-patient versus combined day
hospital treatment of alcoholism: primary and secondary outcome measures.
Weithmann G, Hoffmann M.
Department of Health Services Research, Centre of Psychiatry Weissenau,
University of Ulm, Ravensburg, Germany. gerd.weithmann@zfp-weissenau.de
In Germany, the treatment system for alcoholics is predominantly in-patient (IP)
oriented, but no randomised trials of setting effects have been conducted until
now. We examined if detoxification treatment offered in a day clinic setting
would lead to results comparable to the usual IP treatment. After initial IP
detoxification, patients (n = 109) at a standard withdrawal treatment unit were
randomly assigned to IP or day hospital groups. In both settings, identical
psychosocial treatment was given. In this article, results of primary (percent
days abstinent and drinks per drinking day) and secondary outcome measures
(relapses during treatment, premature termination, additional hospitalisation
during follow-up, percent of voluntary abstinent days and continuous abstinence)
are reported. Outcome measures were assessed quarterly during a 1-year follow-up
period. Patients improved significantly after both treatments, but we found no
significant setting or setting x time interaction effects for any primary or
secondary outcome measure. (c) 2005 S. Karger AG, Basel
-----
BMJ. 2005 Sep 10;331(7516):541.
Effectiveness of treatment for alcohol problems: findings of the
randomised UK alcohol treatment trial (UKATT).
UKATT Research Team.
OBJECTIVE: To compare the effectiveness of social behaviour and network therapy,
a new treatment for alcohol problems, with that of the proved motivational
enhancement therapy. DESIGN: Pragmatic randomised trial. SETTING: Seven
treatment sites around Birmingham, Cardiff, and Leeds. PARTICIPANTS: 742 clients
with alcohol problems; 689 (93.0%) were interviewed at three months and 617
(83.2%) at 12 months. INTERVENTIONS: Social behaviour and network therapy and
motivational enhancement therapy. MAIN OUTCOME MEASURES: Changes in alcohol
consumption, alcohol dependence, and alcohol related problems over 12 months.
RESULTS: Both groups reported substantial reductions in alcohol consumption,
dependence, and problems, and better mental health related quality of life over
12 months. Between groups we found only one significant difference in outcome,
probably due to chance: the social network group showed significantly better
physical health at three months. Non-significant differences at 12 months in the
motivational group relative to the social network group included: the number of
drinks consumed per drinking day had decreased by an extra 1.1 (95% confidence
interval -1.0 to 3.2); scores on the Leeds dependence questionnaire had improved
by an extra 0.6 (-0.7 to 2.0); scores on the alcohol problems questionnaire had
improved by an extra 0.5 (-0.4 to 1.4); but the number of days abstinent from
drinking had increased by 1.2% less (-4.5% to 6.9%). CONCLUSION: The novel
social behaviour and network therapy for alcohol problems did not differ
significantly in effectiveness from the proved motivational enhancement therapy.
-----
Fortschr Neurol Psychiatr. 2005 Sep;73(9):517-25.
[Psychosocial stress and alcohol consumption: interrelations, consequences and
interventions.]
[Article in German]
Walter M, Dammann G, Wiesbeck GA, Klapp BF.
Universitare Psychiatrische Kliniken Basel, Schweiz. marc.walter@upkbs.ch.
BACKGROUND: Psychosocial stress can not only be considered as a result of
chronic alcohol abuse, but also as a cause of high alcohol consumption and it
maintains as a distress syndrome the subsequent course of the alcohol use
disorder. METHODS: This review summarises empirical research results concerning
the interrelations between psychosocial stress and alcohol consumption. The
effects of psychosocial stress are regarded as an ideal-typical process leading
to an increased alcohol intake and later to chronic alcohol abuse, often ending
in alcohol dependence. The aim of the study is to demonstrate the relevance of
stress and distress for diagnostics and therapy of alcohol- related disorders.
RESULTS: At the starting point of high alcohol consumption psychological relief
due to the stress-reducing effects of alcohol is often assumed. A vicious circle
begins, perpetuating psychosocial distress and reinforcing the anxious or
depressive symptoms related to emerging distress syndromes. Associated frequent
comorbidities during the progression are other substance- related disorders,
anxiety and affective disorders. Following alcohol dependence severe somatic and
psychosocial consequences have to be anticipated. CONCLUSIONS: Psychosocial
stress, distress and psychological effects can be understood as an important
psychopathological developmental process of prolonged alcoholism. Symptoms of
distress may be a first relevant evidence of high and hazardous alcohol
consumption. Alcoholic patients should be motivated early to attend psychiatric
and psychotherapeutic treatments to improve their chances for a positive
development. Positive results can be achieved with stress management programs in
alcohol dependent patients. These interventions appear to have comparable
effects to other treatments.
-----
Am J Psychiatry. 2005 Aug;162(8):1423-31.
Anticraving medications for relapse prevention: a possible new class of
psychoactive medications.
O'Brien CP.
University of Pennsylvania/Philadelphia VA Medical Center, Philadelphia, PA
19104-6178, USA. obrien@mail.trc.upenn.edu
Psychiatrists have gradually developed a list of medications that are effective
in the treatment of addictive disorders. Although alcoholism has received the
most attention, nicotine, heroin, and cocaine have all been shown to be
influenced by heredity. Of course, the immediate goal is the reduction of drug
craving and the prevention of relapse to compulsive drug taking. A medication
that can aid in the maintenance of the opiate-free state is naltrexone, a
specific opiate antagonist. Naltrexone is also a good example of an anticraving
medication used in the treatment of alcoholism. Clinicians currently have two
types of medication to aid in the treatment of tobacco use disorder, arguably
the most important addiction. Bupropion and nicotine replacement can be given in
a coordinated fashion to provide the best available results. At present, no
medication is approved by the Food and Drug Administration for the indication of
cocaine addiction. Recently, however, five different medications, already
approved for other purposes, have been found to be effective among cocaine
addicts. Despite clinical trials that show benefit, anticraving medications are
not well known and are underused by clinicians. Addiction is a heterogeneous
condition, with variability in reactivity to the drug of abuse and to the
medications available to treat it. Recent developments in pharmacogenetics may
result in improved selection of medications based on genotype.
-----
Alcohol Clin Exp Res. 2005 Aug;29(8):1432-43.
Follow-up study of anxiety disorder and alcohol dependence in comorbid
alcoholism treatment patients.
Kushner MG, Abrams K, Thuras P, Hanson KL, Brekke M, Sletten S.
Department of Psychiatry, Fairview Riverside Hospital, University of Minnesota,
Minneapolis 55454, USA. kushn001@umn.edu
BACKGROUND: Anxiety disorders are present in a high percentage of alcoholism
treatment patients. We tested the prediction that having a comorbid anxiety
disorder increases the prospective risk for relapse to drinking after alcoholism
treatment. We also explored the prospective associations of specific anxiety
syndromes (and depression) with drinking and anxiety outcomes. METHODS: We
assessed the diagnostic status and daily drinking patterns of 82 individuals
approximately one week after they entered alcoholism treatment (baseline) and
again approximately 120 days later (follow-up) (n=53). RESULTS: Consistent with
study predictions, those with a baseline anxiety disorder (approximately 55%)
were significantly more likely than others to meet various definitions of
drinking relapse over the course of the follow-up. Regression models showed that
baseline social phobia was the single best predictor of a return to any drinking
after treatment, whereas panic disorder was the single best predictor of a
relapse to alcohol dependence after treatment. Having multiple anxiety disorders
(versus any specific anxiety disorder) at the baseline was the strongest
predictor of having at least one active ("persistent") anxiety disorder at the
follow-up. Cross-sectional analysis at the follow-up showed that anxiety
disorder persisted in the absence of a relapse to alcohol dependence far more
often than relapse to alcohol dependence occurred in the absence of a persistent
anxiety disorder. CONCLUSIONS: Screening for comorbid anxiety disorder in
alcoholism treatment patients is warranted and, where found, should be
considered a marker of high relapse risk relative to that of noncomorbid
patients. The capacity of specific anxiety treatment to mitigate relapse risk
among comorbid patients remains an open question.
-----
Arch Intern Med. 2005 Jul 25;165(14):1600-5.
Use of oral topiramate to promote smoking abstinence among alcohol-dependent
smokers: a randomized controlled trial.
Johnson BA, Ait-Daoud N, Akhtar FZ, Javors MA.
Department of Psychiatric Medicine, University of Virginia, Charlottesville
22908-0623, USA. bankolejohnson@virginia.edu
BACKGROUND: Previously, our group has shown that topiramate, a sulfamate-substituted
fructopyranose derivative, is an effective treatment for alcohol dependence.
Herein, we extend that proof-of-concept study by determining whether
cigarette-smoking, alcohol-dependent individuals from the earlier study also
experienced improved smoking outcomes. METHODS: As a subgroup analysis of a
larger double-blind, randomized, controlled, 12-week study comparing topiramate
vs placebo as treatment for alcohol dependence, a 12-week clinical trial
compared topiramate vs placebo in 94 cigarette-smoking, alcohol-dependent
individuals. Of these, 45 were assigned to receive topiramate (escalating dose
from 25 to 300 mg/d) and the remaining 49 had placebo as an adjunct to weekly
standardized medication compliance management. The primary outcome was smoking
cessation ascertained by self-report and confirmed by the level of serum
cotinine (nicotine's major metabolite). RESULTS: Topiramate recipients were
significantly more likely than placebo recipients to abstain from smoking (odds
ratio, 4.46; 95% confidence interval, 1.08-18.39; P = .04). Using a serum
cotinine level of 28 ng/mL or lower to segregate nonsmokers from smokers, we
found that the topiramate group had 4.97 times the odds of being nonsmokers (95%
confidence interval, 1.1-23.4;P = .04). Smoking cessation rates for topiramate
recipients were 19.4% and 16.7% at weeks 9 and 12, respectively, compared with
6.9% at both time points for placebo recipients. CONCLUSION: In this trial,
topiramate (up to 300 mg/d) showed potential as a safe and promising medication
for the treatment of cigarette smoking in alcohol-dependent individuals.
-----
Clin Ther. 2005 Jun;27(6):695-714.
Acamprosate for the treatment of alcohol dependence.
Boothby LA, Doering PL.
Harrison School of Pharmacy, Auburn University, Alabama, USA. lisa.boothby@crhs.net
BACKGROUND: Both inpatient and outpatient treatment centers that focus solely on
psychosocial therapies for the treatment of alcohol dependence have high relapse
rates. Thus, extensive research has focused on the development of pharmacologic
moieties to attenuate the craving for alcohol after acute alcohol
detoxification. Three drug therapies are currently approved by the US Food and
Drug Administration (FDA) for this purpose: disulfiram, naltrexone, and
acamprosate. The latter was approved by the FDA in 2004. OBJECTIVE: This article
describes the pharmacologic properties and clinical usefulness of acamprosate
for the treatment of alcohol dependence. METHODS: Relevant information was
identified through searches of MEDLINE (1966 to March 2005), International
Pharmaceutical Abstracts (1970-2005), Current Contents (1996-2005), and
Cumulative Index to Nursing and Allied Health Literature (1982-Week 2, 2004)
using the key words acamprosate, alcohol dependence, and alcoholism (MeSH).
RESULTS: Acamprosate limited to randomized, controlled clinical trials yielded
33 hits in MEDLINE. Twenty-two articles were reviewed for efficacy end points,
and 10 were reviewed for pharmacology and pharmacokinetics data. Acamprosate
plus pharmacokinetics and pharmacodynamics yielded 19 hits, some of which were
duplicates from the previously described search. Acamprosate plus meta-analysis
(MeSH) yielded 5 hits, naltrexone plus meta-analysis (MeSH) yielded 9 hits, and
disulfiram plus meta-analysis yielded 3 hits. The most recent review articles
and their reference lists were assessed to ensure completeness of literature
searches. Based on these searches, acamprosate is known to be an analogue of
taurine and gamma-aminobutyric acid (GABA), 2 central nervous system
neuromodulators. Acamprosate is thought to share some of the cellular actions of
taurine affecting GABA and glutaminergic receptors in the nucleus accumbens, a
brain region that may be responsible for the reinforcing effects received after
alcohol consumption. Acamprosate is thought to also suppress excitation-induced
calcium entry that results from chronic alcohol exposure, thereby altering the
conformation of the N-methyl-d-aspartate receptors. The percentage of patients
taking acamprosate who were completely abstinent throughout the different
durations of the studies varied from approximately 18% to 61%, compared with 4%
to 45% with placebo. Diarrhea was the most common adverse effect accompanying
acamprosate therapy, and this was generally described as dose related and
transient. CONCLUSIONS: Acamprosate is associated with modest treatment effects.
Its efficacy is similar to naltrexone, and the combination of acamprosate and
naltrexone appears to be more efficacious than acamprosate alone, when combined
with psychosocial interventions.
-----
Rev Med Suisse. 2005 Jun 29;1(26):1728-30, 1732-3.
[Does disulfiram still have a role in alcoholism treatment?]
[Article in French]
Blanc M, Daeppen JB.
CTA-MP16, CHUV, 1011 Lausanne.
What is the place of disulfiram in the treatment of alcohol dependence since
anti-craving pharmacological molecules (acamprosate, naltrexone) were launched
on the market? Considering methodological limitations, available studies do not
allow to conclude about disulfiram's efficacy. Clinical observations indicate
however that disulfiram should keep a place in the treatment of
alcohol-dependence considering favourable outcome for some patients. Disulfiram
implants have however to be avoided. Side effects and possible adverse reactions
should not be a barrier to its use. Disulfiram shouldn't be given during
pregnancy and to patients with instable cardio-vascular disease. Its
prescription justifies a close monitoring of liver tests for patients with
abnormal hepatic function.
-----
Eur Addict Res. 2005;11(4):197-203.
A randomised clinical trial of in-patient versus combined day hospital treatment
of alcoholism: primary and secondary outcome measures.
Weithmann G, Hoffmann M.
Department of Health Services Research, Centre of Psychiatry Weissenau,
University of Ulm, Ravensburg, Germany. gerd.weithmann@zfp-weissenau.de
In Germany, the treatment system for alcoholics is predominantly in-patient (IP)
oriented, but no randomised trials of setting effects have been conducted until
now. We examined if detoxification treatment offered in a day clinic setting
would lead to results comparable to the usual IP treatment. After initial IP
detoxification, patients (n = 109) at a standard withdrawal treatment unit were
randomly assigned to IP or day hospital groups. In both settings, identical
psychosocial treatment was given. In this article, results of primary (percent
days abstinent and drinks per drinking day) and secondary outcome measures
(relapses during treatment, premature termination, additional hospitalisation
during follow-up, percent of voluntary abstinent days and continuous abstinence)
are reported. Outcome measures were assessed quarterly during a 1-year follow-up
period. Patients improved significantly after both treatments, but we found no
significant setting or setting x time interaction effects for any primary or
secondary outcome measure. (c) 2005 S. Karger AG, Basel
-----
BMC Public Health. 2005 Jul 14;5(1):75 [Epub ahead of print]
Are alcoholism treatments effective? The Project MATCH data.
Cutler RB, Fishbain DA.
BACKGROUND: Project MATCH was the largest and most expensive alcoholism
treatment trial ever conducted. The results were disappointing. There were
essentially no patient-treatment matches, and three very different treatments
produced nearly identical outcomes. These results were interpreted post hoc as
evidence that all three treatments were quite effective. We re-analyzed the data
in order to estimate effectiveness in relation to quantity of treatment.
METHODS: This was a secondary analysis of data from a multisite clinical trial
of alcohol dependent volunteers (N= 1726) who received outpatient psychosocial
therapy. Analyses were confined to the primary outcome variables, percent days
abstinent (PDA) and drinks per drinking day (DDD). Overall tests between
treatment outcome and treatment quantity were conducted. Next, three specific
groups were highlighted. One group consisted of those who dropped out
immediately; the second were those who dropped out after receiving only one
therapy session, and the third were those who attended 12 therapy sessions.
RESULTS: Overall, a median of only 3% of the drinking outcome at follow-up could
be attributed to treatment. However this effect appeared to be present at week
one before most of the treatment had been delivered. The zero treatment dropout
group showed great improvement, achieving a mean of 72 percent days abstinent at
follow-up. Effect size estimates showed that two-thirds to three-fourths of the
improvement in the full treatment group was duplicated in the zero treatment
group. Outcomes for the one session treatment group were worse than for the zero
treatment group, suggesting a patient self selection effect. Nearly all the
improvement in all groups had occurred by week one. The full treatment group had
improved in PDA by 62% at week one, and the additional 11 therapy sessions added
only another 4% improvement. CONCLUSION: The results suggest that current
psychosocial treatments for alcoholism are not particularly effective. Untreated
alcoholics in clinical trials show significant improvement. Most of the
improvement which is interpreted as treatment effect is not due to treatment.
Part of the remainder appears to be due to selection effects.
-----
Int J Neuropsychopharmacol. 2005 Jun;8(2):267-80.
Naltrexone for the treatment of alcoholism: a meta-analysis of
randomized controlled trials.
Srisurapanont M, Jarusuraisin N.
Department of Psychiatry, Faculty of Medicine, Chiang Mai University, Amphur
Muang, Chiang Mai 50200, Thailand.
Many trials of naltrexone have been carried out in alcohol-dependent patients.
This paper is aimed to systematically review its benefits, adverse effects, and
discontinuation of treatment. We assessed and extracted the data of
double-blind, randomized controlled trials (RCTs) comparing naltrexone with
placebo or other treatment in people with alcoholism. Two primary outcomes were
subjects who relapsed (including heavy drinking) and those who returned to
drinking. Secondary outcomes were time to first drink, drinking days, number of
standard drinks for a defined period, and craving. All outcomes were reported
for the short, medium, and long term. Five common adverse effects and dropout
rates in short-term treatment were also examined. A total of 2861 subjects in 24
RCTs presented in 32 papers were included. For short-term treatment, naltrexone
significantly decreased relapses [relative risk (RR) 0.64, 95% confidence
interval (CI) 0.51-0.82], but not return to drinking (RR 0.91, 95% CI
0.81-1.02). Short-term treatment of naltrexone significantly increased nausea,
dizziness, and fatigue in comparison to placebo [RRs (95% CIs) 2.14 (1.61-2.83),
2.09 (1.28-3.39), and 1.35 (1.04-1.75)]. Naltrexone administration did not
significantly diminish short-term discontinuation of treatment (RR 0.85, 95% CI
0.70-1.01). Naltrexone should be accepted as a short-term treatment for
alcoholism. As yet, we do not know the appropriate duration of treatment
continuation in an alcohol-dependent patient who responds to short-term
naltrexone administration. To ensure that the real-world treatment is as
effective as the research findings, a form of psychosocial therapy should be
concomitantly given to all alcohol-dependent patients receiving naltrexone
administration.
-----
Eur Addict Res. 2005;11(3):132-7.
Efficacy of an intensive outpatient rehabilitation program in
alcoholism: predictors of outcome 6 months after treatment.
Bottlender M, Soyka M.
Department of Psychiatry, Ludwig Maximilians University, Munich, Germany.
bottlend@psy.med.uni-muenchen.de
Treatment of alcohol-dependent patients was primarily focused on inpatient
settings in the past decades. The efficacy of these treatment programs has been
evaluated in several studies and proven to be sufficient. However, with regard
to the increasing costs in public healthcare systems, questions about
alternative treatment strategies have been raised. Meanwhile, there is growing
evidence that outpatient treatment might be comparably effective as inpatient
treatment, at least for subgroups of alcohol dependents. On that background, the
present study aimed to evaluate the efficacy of a high-structured outpatient
treatment program in 103 alcohol-dependent patients. 74 patients (72%)
terminated the outpatient treatment regularly. At 6 months' follow-up, 95%
patients were successfully located and personally re-interviewed. Analyses
revealed that 65 patients (64%) were abstinent at the 6-month follow-up
evaluation and 37 patients (36%) were judged to be non-abstinent. Pre-treatment
variables which were found to have a negative impact (non-abstinence) on the
6-month outcome after treatment were a higher severity of alcohol dependence
measured by a longer duration of alcohol dependence, a higher number of prior
treatments and a stronger alcohol craving (measured by the Obsessive Compulsive
Drinking Scale). Further patients with a higher degree of psychopathology
measured by the Beck Depression Inventory (depression) and State-Trait Anxiety
Inventory (anxiety) relapsed more often. In summary, results of this study
indicate a favorable outcome of socially stable alcohol-dependent patients and
patients with a lower degree of depression, anxiety and craving in an intensive
outpatient rehabilitation program.
-----
Drug Alcohol Depend. 2005 May 5; [Epub ahead of print]
Outpatient alcoholism treatment: Predictors of outcome after 3
years.
Bottlender M, Soyka M.
Department of Psychiatry, Ludwig-Maximilians University, Munich, Nussbaumstr. 7,
80336 Munich, Germany.
AIMS:: This prospective study investigated predictors for relapse 3 years after
completion of an intensive outpatient treatment programme for alcoholism.
DESIGN:: As previous studies mainly revealed that severity of alcohol
dependence, and comorbid psychopathology were predictive for subsequent
relapses, the impact of these and other pre-treatment variables on the 36-month
outcome was evaluated in a logistic regression analysis. A structured interview
was used to assess the variables. Patients were personally interviewed at entry
to, and the end of, an outpatient treatment programme, and 6, 12, 24 and 36
months after the end of treatment. One hundred and three alcohol-dependent
participants who were taking part in an outpatient treatment were consecutively
recruited. RESULTS:: Seventy-four patients completed the treatment programme. At
the follow-up after 36 months, 2 patients had died (after heavy alcohol relapse)
and 88 (88%) of the remaining patients could be located and personally
re-interviewed. Forty-four (43%) patients were abstinent, 46 (45%) had relapsed
and 12 (12%) were classified as improved for the total follow-up period
according to the classification proposed by Feuerlein and Kufner. Based on a
logistic regression analysis, significant variables for prediction of relapse
were treatment drop-outs, female sex and sum of positive life events prior to
treatment (relapsers had significantly fewer positive life events).
CONCLUSIONS:: In contrast to previous studies we could not confirm the
importance of determinants known as risk factors for relapse like severity of
alcohol dependence. The strongest predictor for relapsing after treatment is
treatment drop-out. Since women were at an increased risk for relapse
gender-specific treatment approaches should be considered. In summary, the
effectiveness of the studied intensive outpatient treatment programme, with an
abstinence rate of 43% for the total follow-up period of 3 years, is favourable
although selection criteria of must be taken into account.
-----
Biol Psychiatry. 2005 May 15;57(10):1128-37.
Naltrexone and disulfiram in patients with alcohol dependence and
comorbid psychiatric disorders.
Petrakis IL, Poling J, Levinson C, Nich C, Carroll K, Rounsaville B; VA New
England VISN I MIRECC Study Group.
Department of Psychiatry, Yale University, New Haven, Connecticut 06516, USA.
ismene.petrakis@yale.edu
BACKGROUND: Disulfiram and naltrexone are approved by the Food and Drug
Administration (FDA) for the treatment of alcoholism, but these agents have not
been rigorously evaluated in dually diagnosed individuals. METHOD: Two-hundred
and fifty-four patients with an Axis I psychiatric disorder and comorbid alcohol
dependence were treated for 12 weeks in an outpatient medication study conducted
at three Veterans Administration outpatient clinics. Randomization included
assignment to one of four groups: 1) naltrexone alone; 2) placebo alone; 3)
(open-label) disulfiram and (blinded) naltrexone; or 4) (open-label) disulfiram
and (blinded) placebo. Medication compliance was evaluated using the
Microelectric Events Monitoring System. Primary outcomes were measures of
alcohol use. Secondary outcomes included psychiatric symptoms, alcohol craving,
g-GGT levels and adverse events. RESULTS: There was a high rate of abstinence
across groups. Subjects treated with an active medication had significantly more
consecutive weeks of abstinence and less craving than those treated with
placebo, but there were no significant group differences in other measures of
alcohol consumption. There was no advantage of the combination of both
medications. CONCLUSIONS: These data suggest a modest advantage for the use of
disulfiram and naltrexone for this group of dually diagnosed alcohol-dependent
individuals but did not suggest an advantage in the combination.
-----
Expert Opin Investig Drugs. 2005 Apr;14(4):371-6.
Novel anticonvulsants in the treatment of alcoholism.
Book SW, Myrick H.
Medical University of South Carolina, Department of Psychiatry and Behavioural
Sciences, Charleston Alcohol Research Center, 67 President Street, Charleston,
SC 29425, USA. booksw@musc.edu
There have been many recent developments in the pharmacological management of
alcohol withdrawal and alcohol dependence. Although previous treatments had
included benzodiazepines as their mainstay, the use of these agents in the
alcoholic population is problematic. Benzodiazepines are themselves addictive
and they may increase the risk of alcohol relapse. Non-benzodiazepine
anticonvulsants such as carbamazepine, valproic acid, gabapentin, vigabatrin and
topiramate have been shown to be excellent treatments of both alcohol withdrawal
and the prevention of alcohol relapse. Although none of these agents have yet
been approved by the FDA, there is growing evidence in the literature to support
their use.
-----
JAMA. 2005 Apr 6;293(13):1617-25.
Efficacy and tolerability of long-acting injectable naltrexone
for alcohol dependence: a randomized controlled trial.
Garbutt JC, Kranzler HR, O'Malley SS, Gastfriend DR, Pettinati HM, Silverman BL,
Loewy JW, Ehrich EW; Vivitrex Study Group.
Department of Psychiatry, University of North Carolina School of Medicine,
Chapel Hill 27599-7160, USA. jc_garbutt@med.unc.edu
CONTEXT: Alcohol dependence is a common disorder associated with significant
morbidity and mortality. Naltrexone, an opioid antagonist, has been shown to be
effective for treatment of alcohol dependence. However, adherence to daily oral
pharmacotherapy can be problematic, and clinical acceptance and utility of oral
naltrexone have been limited. OBJECTIVE: To determine efficacy and tolerability
of a long-acting intramuscular formulation of naltrexone for treatment of
alcohol-dependent patients. DESIGN, SETTING, AND PARTICIPANTS: A 6-month,
randomized, double-blind, placebo-controlled trial conducted between February
2002 and September 2003 at 24 US public hospitals, private and Veterans
Administration clinics, and tertiary care medical centers. Of the 899
individuals screened, 627 who were diagnosed as being actively drinking
alcohol-dependent adults were randomized to receive treatment and 624 received
at least 1 injection. INTERVENTION: An intramuscular injection of 380 mg of
long-acting naltrexone (n = 205) or 190 mg of long-acting naltrexone (n = 210)
or a matching volume of placebo (n = 209) each administered monthly and combined
with 12 sessions of low-intensity psychosocial intervention. MAIN OUTCOME
MEASURE: The event rate of heavy drinking days in the intent-to-treat
population. RESULTS: Compared with placebo, 380 mg of long-acting naltrexone
resulted in a 25% decrease in the event rate of heavy drinking days (P = .02)
[corrected] and 190 mg of naltrexone resulted in a 17% decrease (P = .07). Sex
and pretreatment abstinence each showed significant interaction with the
medication group on treatment outcome, with men and those with lead-in
abstinence both exhibiting greater treatment effects. Discontinuation due to
adverse events occurred in 14.1% in the 380-mg and 6.7% in the 190-mg group and
6.7% in the placebo group. Overall, rate and time to treatment discontinuation
were similar among treatment groups. CONCLUSIONS: Long-acting naltrexone was
well tolerated and resulted in reductions in heavy drinking among
treatment-seeking alcohol-dependent patients during 6 months of therapy. These
data indicate that long-acting naltrexone can be of benefit in the treatment of
alcohol dependence.
-----
Alcohol Alcohol. 2005 Mar 29; [Epub ahead of print]
Clinical predictors of response to Naltrexone in alocoholic
patients: Who benefits most from treatment with Naltrexone?
Rubio G, Ponce G, Rodriguez-Jimenez R, Jimenez-Arriero MA, Hoenicka J, Palomo T.
Alcoholism Research Program, Servicios de Salud Mental, Retiro, Madrid, Spain.
AIMS: To determine the clinically ascertained variables that are related to
satisfactory response to naltrexone (NTX) treatment of alcohol dependence after
detoxification. METHODS: The use of intake and outcome variables were measured
in a randomized 3-month open-controlled trial comparing the effects of
naltrexone plus psychotherapy treatment versus psychotherapy treatment alone on
the maintenance of abstinence in the final 28 days (n = 336, all male). RESULTS:
Predictors of a positive response to NTX treatment were family history of
alcoholism (P = 0.010), early age at onset of drinking problems (P = 0.014) and
comorbid use of other drugs of abuse (P < 0.001). Among the subjects not treated
with NTX, the greater the number of predictor variables, the lower the final 28
days abstinence rates (P = 0.00003), but this was not the case in patients
treated with NTX (P = 0.844). CONCLUSIONS: Patients with these features,
suggesting biological vulnerability overall have poorer outcomes, but this can
be reduced with NTX treatment. The type of alcoholism should be considered
before deciding on the pharmacological strategy.
-----
Fortschr Neurol Psychiatr. 2005 Mar;73(3):150-5.
[Catamnestic study on the efficacy of an intensive outpatient
treatment programme for alcohol-dependent patients: impact of participation in
AA on the abstinence rates]
[Article in German]
Bottlender M, Soyka M.
Psychiatrische Klinik und Poliklinik, Ludwig-Maximilians-Universitat Munchen,
Deutschland. bottlend@psy.med.uni-muenchen.de
This study analyzed the Alcoholics Anonymous participation and the impact on the
abstinence rate of 103 alcohol dependent patients (ICD-10) during the 24 months
after their discharge from high-structured out-patient treatment. The treatment
retention amounted to n = 74 (72 %), 18 of the 25 dropouts took place because of
alcohol relapse. At 6-, 12- and 24-months-follow-up 87 - 95 % of the patients
were successfully located and re-interviewed. Analyses revealed that 64 % of the
patients were abstinent at the 6-months-follow-up evaluation, 56 % at the total
12-months-follow-up evaluation. 49 % of the patients remained abstinent until
the 24-months-follow-up evaluation, 14 % were improved and 37 % relapsed. 56
patients (55 %) participated in selfhelp-groups the first six months following
treatment, two years later 45 patients (44 %) still attended a group. 53 - 56 %
participated on a weekly basis. Patients who participated regularly on a weekly
basis in self-help-groups fared the best on 2-year outcome. Patients who
infrequently at all participated or not had the poorest outcome (relapse). After
controlling for confounding variables (sex, treatment drop-out, relapse during
treatment) these results were still statistical significant. Results indicate
the predictive value of AA attendance for relapse prevention after controlling
for confounding variables. The value of self-help-groups in the network of
alcoholism treatment is discussed.
-----
Eur Addict Res. 2005;11(2):83-91.
Pharmacological relapse prevention of alcoholism: clinical
predictors of outcome.
Kiefer F, Helwig H, Tarnaske T, Otte C, Jahn H, Wiedemann K.
Department of Addictive Behaviour and Addiction Medicine, Central Institute of
Mental Health (CIMH), University of Heidelberg, Heidelberg, Germany.
Objective: The efficacy of pharmacological relapse prevention in alcoholism with
acamprosate and naltrexone has been supported by several controlled trials. It
remains uncertain whether any differential indication for treatment exists.
Methods: We evaluated outcome data of a controlled trial on acamprosate and
naltrexone in patients with low vs. high baseline somatic distress, depression
and anxiety (Symptom Checklist-90, SCL-90), low vs. high baseline craving, and
according to typological differentiation as proposed by Cloninger and Lesch.
These variables have previously been suggested to be predictors of outcome.
Results: Comparing the course of abstinence rates, acamprosate was mainly
efficacious in patients with low baseline somatic distress, whereas naltrexone
was effective especially in patients with high baseline depression. Baseline
craving showed no predictive value. Pharmacological treatment was efficacious in
type II alcoholics according to Cloninger. Applying Lesch's typological
differentiation, acamprosate was shown to be mainly effective in type I, whereas
naltrexone revealed best treatment effects in type III and IV. Conclusion: The
study supports the hypothesis that different subgroups of alcohol dependent
subjects might benefit from a differential treatment with either naltrexone or
acamprosate. Baseline psychopathology and especially typological differentiation
might be useful in matching patients to distinct pharmacotherapeutic
interventions. Copyright (c) 2005 S. Karger AG, Basel.
-----
Alcohol Clin Exp Res. 2005 Feb;29(2):278-86.
New developments in prevention and early intervention for alcohol
abuse in youths.
Stewart SH, Conrod PJ, Marlatt GA, Comeau MN, Thush C, Krank M.
Department of Psychology, Dalhousie University, Halifax, Nova Scotia, Canada.
This article summarizes a symposium held at the 2004 Annual Meeting of the
Research Society on Alcoholism in Vancouver, British Columbia, Canada. It was
prepared by the conference co-organizers/co-chairs with substantial input from
each of the symposium participants. Increasingly, alcohol abuse interventions
focus on preventing alcohol problems or intervening early before risky drinking
behavior becomes ingrained. Universal prevention programs have produced no or
only modest effects on the drinking behavior of youths. Although some existing
targeted prevention programs have proved effective, they have not tapped the
full range of potential intervention targets, such as the underlying motivations
for alcohol misuse in youths who are at greatest risk. The set of papers
presented in this symposium outline exciting new developments in the field of
targeted prevention and early intervention programs for adolescent drinking
problems, presented by an international panel of researchers. These developments
include attention to making interventions relevant to adolescents' lives, focus
on personality and motivational factors underlying alcohol misuse, and combining
existing cognitive behavioral programs with expectancy challenge and
motivational interviewing techniques.
-----
Arch Gen Psychiatry. 2005 Feb;62(2):199-207.
The effectiveness of telephone-based continuing care for alcohol
and cocaine dependence: 24-month outcomes.
McKay JR, Lynch KG, Shepard DS, Pettinati HM.
Department of Psychiatry, University of Pennsylvania, Philadelphia 19104, USA.
mckay_j@mail.trc.upenn.edu <mckay_j@mail.trc.upenn.edu>
CONTEXT: Telephone-based disease management protocols have shown promise in
improving outcomes in a number of medical and psychiatric disorders, but this
approach to continuing care has received little study in alcohol- and
drug-dependent individuals. OBJECTIVE: To compare telephone-based continuing
care with 2 more intensive face-to-face continuing care interventions. DESIGN: A
randomized 3-group clinical trial with a 2-year follow-up. SETTING: Two
outpatient substance abuse treatment programs, one community-based and the other
at a Veterans Affairs medical center facility. PATIENTS: Alcohol- and/or
cocaine-dependent patients (N = 359) who had completed 4-week intensive
outpatient programs. INTERVENTIONS: Three 12-week continuing care treatments:
weekly telephone-based monitoring and brief counseling contacts combined with
weekly supportive group sessions in the first 4 weeks (TEL), twice-weekly
cognitive-behavioral relapse prevention (RP), and twice-weekly standard group
counseling (STND). MAIN OUTCOME MEASURES: Percentage of days abstinent from
alcohol and cocaine, total abstinence from alcohol and cocaine, negative
consequences of substance use, cocaine urine toxicological results, and gamma-glutamyltransferase.
RESULTS: Participants in TEL had higher rates of total abstinence over the
follow-up than those in STND (P<.05). In alcohol-dependent participants,
24-month gamma-glutamyltransferase levels were lower in TEL than in RP (P =
.005). In cocaine-dependent participants, there was a significant group x time
interaction (P = .03) in which the rate of cocaine-positive urine samples
increased more rapidly in RP as compared with TEL. On percentage of days
abstinent or negative consequences of substance use, TEL did not differ from RP
or STND. Participants with high scores on a composite risk indicator, based on
co-occurring alcohol and cocaine dependence and poor progress toward achieving
intensive outpatient program goals, had better total abstinence outcomes up to
21 months if they received STND rather than TEL, whereas those with lower scores
had higher abstinence rates in TEL than in STND (P = .04). CONCLUSIONS:
Telephone-based continuing care appears to be an effective form of step-down
treatment for most patients with alcohol and cocaine dependence who complete an
initial stabilization treatment, compared with more intensive face-to-face
interventions. However, high-risk patients may have better outcomes if they
first receive group counseling continuing care after completing intensive
outpatient programs.
-----
Actas Esp Psiquiatr. 2005 Jan;33(1):13-18.
[Efficacy of naltrexone in the treatment of alcohol dependence
disorder in women.]
[Article in Spanish]
Ponce G, Sanchez-Garcia J, Rubio G, Rodriguez-Jimenez R, Jimenez-Arriero M,
Palomo T.
Servicio de Psiquiatria. Hospital Doce de Octubre. Madrid.
Alcoholism is a major public health problem. Although its prevalence is higher
in men, the clinical and social repercussions of alcoholism in women are also of
great concern, as they have differential characteristics in different
vulnerability, and thus therapeutic implications. In recent years, we have seen
an increase of the percentages of women with problems related to alcohol
consumption in Spain. Several pharmacological treatments as the antagonist of
the opioid receptors naltrexone have demonstrated efficacy in the treatment of
dehabituation of alcoholism in males, however, there are no studies in the
female population. This report is the first randomized study about the efficacy
of naltrexone in the treatment of dehabituation in women with alcohol dependence
disorder. Methods. In a 12 week, single-blind, randomized trial, we studied 100
women with alcohol dependence disorder (DSM-IV), evaluating the efficacy of
adding naltrexone as adjunctive treatment to the dehabituation treatment.
Results. The naltrexone group showed a lower rate of alcohol relapse during the
follow-up period (76 % vs. 46%; ?2=8.239; p=0.004), and significantly lower
dropout rates (16% vs. 38 %; ?2=5.074; p=0.024). We also found a lower number of
days of intoxication (2.88 vs. 14.64; t=2.732; p=0.011). Conclusions. Naltrexone
shows efficacy as adjunctive treatment to maintain abstinence in women with
alcohol dependence disorder. Further studies are needed to confirm the efficacy
of this treatment and to find specific predictors of good outcome in women.
Actas Esp Psiquiatr 2005;33(1):13-18.
-----
Harv Rev Psychiatry. 2004 Nov-Dec;12(6):351-66.
Pharmacotherapy for alcohol-related disorders: what clinicians
should know.
Mariani JJ, Levin FR.
Department of Psychiatry, Division on Substance Abuse, Columbia University,
College of Physicians and Surgeons, USA. Mariani@pi.cpmc.columbia.edu
Alcohol-related disorders are a major public health problem in the United
States. Alcohol interacts with several neurotransmitter systems causing both
acute and chronic effects in the brain. While the mainstay of treatment of
alcohol-related disorders, with the exception of alcohol withdrawal, has
historically been psychosocial, pharmacotherapy is increasingly being
investigated and incorporated into standard clinical practice. Patients with
alcohol use disorders and comorbid psychiatric conditions, most commonly
depressive and anxiety disorders, can benefit from symptom-targeted
pharmacotherapy, even if the patient fails to achieve abstinence from alcohol.
Although benzodiazepines remain the treatment of choice to treat alcohol
withdrawal, a variety of other agents is being investigated, particularly in the
outpatient setting. Further randomized clinical trials of alcohol-related
disorder pharmacotherapy, particularly of comorbid subpopulations, are needed to
better inform clinical decision making. The routine exclusion of
alcohol-dependent patients from pharmacotherapy trials of psychiatric disorders
presents a barrier to gathering more data. Recommendations for future research
are discussed.
-----
Curr Psychiatry Rep. 2004 Oct;6(5):332-8.
Recent advances in the pharmacotherapy of alcoholism.
Myrick H, Anton R.
Alcohol Research Center, Medical University of South Carolina Department of
Psychiatry and Behavioral Sciences, 67 President Street, Charleston, SC 29425,
USA. myrickh@musc.edu
Alcoholism is a devastating illness that leads to great societal losses. Despite
significant health consequences, there are few medically based treatments for
alcoholism. During the past decade, a better understanding of the
neuroscientific underpinnings of addiction has led to the use of novel
pharmacotherapeutic treatments for alcoholism. In particular, there have been
new developments in the understanding of the involvement of the dopamine,
opiate, serotonin, gamma-aminobutyric acid, and glutamate neurotransmitter
systems in the pathophysiology of alcohol withdrawal, alcohol dependence, and in
subtypes of individuals with alcoholism. In this article, new developments in
the pharmacotherapy of alcohol dependence will be reviewed. In particular, the
use of anticonvulsants in alcohol withdrawal and protracted abstinence syndromes
will be discussed. Data on naltrexone, acamprosate, and topiramate will be
highlighted. In addition, data concerning the use of serotonin reuptake
inhibitors in subtypes of alcoholism and the use of combination pharmacotherapy
will be reviewed.
-----
Alcohol Alcohol. 2004 Sep 29 [Epub ahead of print]
Combined therapy: what does Acamprosate and Naltrexone
combination tell us?
Kiefer F, Wiedemann K.
Department of Psychiatry, University Hospital of Hamburg, Hamburg, Germany.
AIMS: Relapse prevention treatment with both acamprosate and naltrexone has been
shown to be efficacious in the treatment of alcoholism. Whereas both compounds
act pharmacologically differently, there is up to now only limited evidence as
to whether combined treatment is efficacious and pharmacologically safe. It
remains to be answered whether data justify the combination of both drugs in
clinical practice. METHODS: Review of the three pre-clinical and four clinical
studies that have been published to date on either combined tolerability or
efficacy. RESULTS: Data available up to now show no occurrence of severe adverse
events during combined treatment. Diarrhoea and nausea were shown to be the most
significant side-effects. Whereas pre-clinical studies regarding efficacy of
combined treatment are not yet conclusive, clinical data show the superiority of
combined treatment compared with both placebo and acamprosate monotherapy. The
synergistic effect of combined treatment remained after 12 weeks of drug-free
follow-up. CONCLUSIONS: The combination of acamprosate with naltrexone in a
clinical sample seems to be efficacious and safe. Numerous alcohol dependent
patients could benefit, particularly those that responded insufficiently on
monotherapeutic treatment with either acamprosate or naltrexone.
-----
Alcohol Clin Exp Res. 2004 Sep;28(9):1362-70.
Effects of naltrexone and nalmefene on subjective response to
alcohol among non-treatment-seeking alcoholics and social drinkers.
Drobes DJ, Anton RF, Thomas SE, Voronin K.
Charleston Alcohol Research Center, Department of Psychiatry and Behavioral
Sciences, Medical University of South Carolina, Charleston, South Carolina, USA.
drobesdj@moffitt.usf.edu
BACKGROUND: Despite the relative success of opiate antagonist medication within
controlled clinical trials for alcoholism, laboratory studies have not fully
examined potential mechanisms for their efficacy in alcohol-dependent persons.
The present study evaluated the impact of naltrexone and nalmefene on craving
and subjective effects after a moderate alcohol dose among non-treatment-seeking
alcoholics (n = 125) and social drinkers (n = 90). METHODS: Participants were
randomly assigned to receive placebo, naltrexone (titrated to 50 mg/day), or
nalmefene (titrated to 40 mg/day) for seven days before an alcohol challenge
clinical laboratory session. During the clinical laboratory session, a drink of
alcohol (0.4 mg/kg for men, 0.34 mg/kg for women) was provided in a bar-like
setting. The effects of the alcohol dose on subjective craving, stimulation, and
sedation were measured before having free access to alcohol. RESULTS: Alcoholics
reported higher levels of craving than social drinkers before and after the
drink as well as higher levels of alcohol-induced stimulation. Both opiate
antagonist medications suppressed initial increases in craving and stimulation.
CONCLUSIONS: These findings demonstrate that both naltrexone and nalmefene are
associated with reduced alcohol-induced craving and stimulation among alcoholics
who are not actively attempting to reduce drinking. These data provide insights
into potential mechanisms that may underlie opiate antagonists' effects in the
context of treatment.
-----
Arch Gen Psychiatry. 2004 Sep;61(9):905-12.
Oral topiramate reduces the consequences of drinking and improves
the quality of life of alcohol-dependent individuals: a randomized controlled
trial.
Johnson BA, Ait-Daoud N, Akhtar FZ, Ma JZ.
Department of Psychiatry, The University of Texas Health Science Center at San
Antonio, 78229-3900, USA. bjohnson@uthscsa.edu
BACKGROUND: Topiramate, a fructopyranose derivative, was superior to placebo at
improving the drinking outcomes of alcohol-dependent individuals. OBJECTIVES: To
determine whether topiramate, compared with placebo, improves psychosocial
functioning in alcohol-dependent individuals and to discover how this
improvement is related to heavy drinking behavior. DESIGN: Double-blind,
randomized, controlled, 12-week clinical trial comparing topiramate vs placebo
for treating alcohol dependence (1998-2001). PARTICIPANTS: One hundred fifty
alcohol-dependent individuals, diagnosed using the DSM-IV. INTERVENTIONS:
Seventy-five participants received topiramate (escalating dose of 25 mg/d to 300
mg/d), and 75 had placebo and weekly standardized medication compliance
management. MAIN OUTCOME MEASURES: Three elements of psychosocial functioning
were measured: clinical ratings of overall well-being and alcohol-dependence
severity, quality of life, and harmful drinking consequences. Overall well-being
and dependence severity and quality of life were analyzed as binary responses
with a generalized estimating equation approach; harmful drinking consequences
were analyzed as a continuous response using a mixed-effects, repeated-measures
model. RESULTS: Averaged over the course of double-blind treatment, topiramate,
compared with placebo, improved the odds of overall well-being (odds ratio [OR]
= 2.17; 95% confidence interval [CI], 1.16-2.60; P =.01); reported abstinence
and not seeking alcohol (OR = 2.63; 95% CI, 1.52-4.53; P =.001); overall life
satisfaction (OR = 2.28; 95% CI, 1.21-4.29; P =.01); and reduced harmful
drinking consequences (OR = -0.07; 95% CI, -0.12 to -0.02, P =.01). There was a
significant shift from higher to lower drinking quartiles on percentage of heavy
drinking days, which was associated with improvements on all measures of
psychosocial functioning. CONCLUSIONS: As an adjunct to medication compliance
enhancement treatment, topiramate (up to 300 mg/d) was superior to placebo at
not only improving drinking outcomes but increasing overall well-being and
quality of life and lessening dependence severity and its harmful consequences.
-----
Am J Clin Hypn. 2004 Jul;47(1):21-8.
Intensive therapy: utilizing hypnosis in the treatment of
substance abuse disorders.
Potter G.
greg@gpotter.com
Hypnosis was once a viable treatment approach for addictions. Then, due to
hypnosis being used for entertainment purposes many professionals lost
confidence in it. However, it has now started to make a comeback in the
treatment of substance abuse. The approach described here, using hypnosis for
treatment, is borrowed from studies effectively treating alcoholism by using
intensive daily sessions. Combining the more intense treatment of 20 daily
sessions with hypnosis is a successful method to treat addictions. The treatment
has been used with 18 clients over the last 7 years and has shown a 77 percent
success rate for at least a 1-year follow-up.
-----
Zh Nevrol Psikhiatr Im S S Korsakova. 2004;104(7):43-9.
[New data on sensibilizing therapy of alcoholic dependence]
[Article in Russian]
[No authors listed]
Lidevine was used in the treatment of 29 patients with chronic alcoholism with
unsatisfactory results of previous therapy. The drug was included in the complex
therapy at the stage of developing therapeutic remission and during a long-term
(1 year) antirelapse treatment. Remission of 1-year duration was achieved in 12
(41%) patients. Use of lidevine contributes to remission stabilization and
prevents development of alcoholism relapse after a single "break down". The
importance of lidevine assignment in combination with psychopharmacological
drugs reducing a drive for alcohol (antidepressants, anticonvulsants-normotimics,
neuroleptics with sedative action, etc.), and a need of continuous control of
the relatives of the patient over the intake of sensibilazing drug are proved.
Good tolerance to the medication is shown.
-----
Zh Nevrol Psikhiatr Im S S Korsakova. 2004;104(7):50-3.
[The efficacy of calcium channel blockers in the treatment of
affective disorders and pathologic drive for alcohol in patients with alcoholism
in remission period]
[Article in Russian]
[No authors listed]
Forty three patients with chronic alcoholism of stage II with secondary
affective disorders (anxiety, subdepression) and actualization of pathological
drive for alcohol in remission period were divided into 3 groups: patients were
treated with nimodipine (90 mg/day during 10 days), patients were treated with
nifedipine (45 mg/day during 10 days) and patients of control group (they
received a placebo for 10 days). The study was double blind. The results
revealed that both calcium channels antagonists reduced a level of depression
measured with the Hamilton scale and Zung test. Ten-day nimodipine (but not
nifedipine) course also caused a significant decrease of anxiety evaluated by
the Spilberger test. Both medications, being significantly more efficient
comparing to placebo, led to desactualization of pathological drive for alcohol
in parallel with affective disorders reduction. Because of the absence of the
depriming effect of these compounds on CNS as well as of dependence phenomenon,
calcium channels antagonists may be used in narcology for stopping secondary
affective disorders and actualization of pathological drive for alcohol in
remission period.
-----
Addict Behav. 2004 Aug;29(6):1253-8.
Naltrexone and brief counseling to reduce heavy drinking in
hazardous drinkers.
Davidson D, Saha C, Scifres S, Fyffe J, O'Connor S, Selzer C.
Department of Psychiatry, School of Medicine, Institute of Psychiatric Research,
Indiana University, 791 Union Drive Indianapolis, IN 46202-4887, USA.
The present study examined the utility of daily naltrexone for decreasing
alcohol drinking in hazardous drinkers. Forty-one participants participated in a
10-week trial and received 30 min of brief counseling on the first and second
week of treatment, as well as a daily dose of 50 mg of naltrexone throughout the
trial. Overall, naltrexone-treated participants did not show the same degree of
improvement on drinking outcomes as placebo-treated participants. The placebo
group drank fewer drinks per drinking day and achieved more abstinence days than
the naltrexone group. Craving was also lower for the placebo group. The groups
were not balanced on gender or family history of alcoholism and this may explain
the lack of effect of naltrexone on the drinking outcomes.
-----
CNS Drugs. 2004;18(9):547-60.
What place does naltrexone have in the treatment of alcoholism?
Rohsenow DJ.
Providence Veterans Affairs Medical Center and Center for Alcohol and Addiction
Studies, Brown University, Providence, Rhode Island, USA.
Despite two recent negative trials, most controlled clinical studies have found
that when naltrexone is added to substance abuse treatment or counselling,
significantly less heavy drinking is done by the patients who are willing to
take most of the prescribed naltrexone. Naltrexone also reduces urges to drink
and makes any slips back into drinking less pleasant. Therefore, naltrexone can
be a useful adjunct to substance abuse counselling or rehabilitation programmes,
as one of many tools that clinicians and patients use. However, beneficial
effects are limited in scope. Naltrexone mostly does not increase the chance of
staying completely abstinent but rather reduces the intensity or frequency of
any drinking that does occur. Many alcohol-dependent individuals are medically
ineligible or are unwilling to take naltrexone, many who start naltrexone do not
continue with it and many who comply with it do not benefit. Compliance is
greater for individuals who experience fewer adverse effects and who have
stronger beliefs in the benefits of naltrexone, suggesting that clinicians can
increase compliance by helping patients to manage adverse effects and by
bolstering patients' beliefs in the benefits of naltrexone. Alcohol-dependent
individuals who are most likely to benefit from naltrexone seem to be those with
close relatives who also had alcohol problems, or who have stronger urges to
drink or who are more limited in cognitive abilities. Some individuals may
benefit from a higher dose, particularly people with lower blood concentrations
of the medication, and individuals who achieve good results may benefit from a
longer course of treatment with naltrexone. In these ways, treatment can be
targeted to increase the likelihood of beneficial outcomes with naltrexone.
-----
CNS Drugs. 2004;18(8):485-504.
Pharmacotherapy of alcohol dependence: a review of the clinical
data.
Mann K.
Department of Addictive Behaviour and Addiction Medicine, Central Institute of
Mental Health, University of Heidelberg, Mannheim, Germany.
Over the last 20 years, the role of adjuvant pharmacotherapy in optimising
outcome in rehabilitation programmes for alcohol-dependent patients has become
increasingly evident. New avenues for rational drug treatment have arisen from
better understanding of the neurobiological substrates of alcohol dependence,
including adaptive changes in amino acid neurotransmitter systems, stimulation
of dopamine and opioid peptide systems, and, possibly, changes in serotonergic
activity. Disulfiram, naltrexone and acamprosate are currently the only
treatments approved for the management of alcohol dependence. However, there is
still no unequivocal evidence from randomised controlled clinical trials that
disulfiram improves abstinence rates over the long term. Aversive therapy with
disulfiram is not without risk for certain patients, and should be closely
supervised. Both naltrexone and acamprosate improve outcome in rehabilitation of
alcohol-dependent patients, but seem to act on different aspects of drinking
pathology. Naltrexone is thought to decrease relapse to heavy drinking by
attenuating the rewarding effects of alcohol. However, data from the naltrexone
clinical trial programme are somewhat inconsistent, with several large studies
being negative. Acamprosate is believed to maintain abstinence by blocking the
negative craving that alcohol-dependent patients experience in the absence of
alcohol. The clinical development programme has involved a large number of
patients and studies, of which the vast majority have shown a beneficial effect
of acamprosate on increasing abstinence rates. Both drugs are generally well
tolerated; nausea is reported by around 10% of patients treated with naltrexone,
while the most frequent adverse effect reported with acamprosate is diarrhoea.
Another opioid receptor antagonist, nalmefene, has shown promising activity in
pilot studies, and may have a similar profile to naltrexone. Data from studies
of SSRIs in alcohol dependence are somewhat heterogeneous, but it appears that
these drugs may indirectly improve outcome by treating underlying depression
rather than affecting drinking behaviour per se. Similarly, the anxiolytic
buspirone may act by ameliorating underlying psychiatric pathology. Dopaminergic
neuroleptics, benzodiazepines and antimanic drugs have not yet demonstrated
evidence of activity in large controlled clinical trials. Trials with drugs
acting at serotonin receptors have yielded disappointing results, with the
possible exception of ondansetron. Because the biological basis of alcohol
dependence appears to be multifactorial, the future of management of alcoholism
may be combination therapy, using drugs acting on different neuronal pathways,
such as acamprosate and naltrexone. Pharmacotherapy should be used in
association with appropriate psychosocial support and specific treatment
provided for any underlying psychiatric comorbidities.
-----
Alcohol Clin Exp Res. 2004 May;28(5):736-45.
A double-blind, placebo-controlled study of olanzapine in the
treatment of alcohol-dependence disorder.
Guardia J, Segura L, Gonzalvo B, Iglesias L, Roncero C, Cardus M, Casas M.
Addictive Behavior Unit, Department of Psychiatry, Hospital de la Santa Creu i
Sant Pau, Barcelona, Spain. jgaurdia@hsp.santpau.es
BACKGROUND: A 12-week, double-blind, randomized, parallel-group clinical trial,
comparing olanzapine and placebo treatment together with cognitive-behavioral
psychotherapy, was carried out to determine the efficacy, safety, and
tolerability of olanzapine in the treatment of alcoholism. METHODS: A total of
60 alcohol-dependent patients were assigned to 12 weeks' treatment with either
olanzapine or placebo. The primary variable relapse to heavy drinking rate was
evaluated by means of intention-to-treat analyses. Alcohol consumption, craving,
adverse events, and changes in the biochemical markers of heavy drinking and
possible toxicity were also evaluated. RESULTS: We did not find significant
differences in the survival analysis between placebo and olanzapine-treated
patients (Kaplan-Meier log rank = 0.46, df = 1, p = 0.50). Eleven (37.9%)
patients treated with olanzapine relapsed compared with 9 (29%) of those
receiving placebo (chi = 0.53, df = 1, p = 0.5). Although some adverse events
(weight gain, increased appetite, drowsiness, constipation, and dry mouth) were
found more frequently in the olanzapine group, differences did not reach
statistical significance in comparison with the placebo group. CONCLUSIONS:
Olanzapine was well tolerated, as the rate of adverse events was low, and it was
safe, because it did not interfere with the normalization of biochemical markers
of heavy drinking or alter liver function markers. Alcohol-dependent patients
showed good adherence and compliance with the treatment protocol, but we found
no differences in relapse rate or other drinking variables when comparing
olanzapine with placebo-treated patients.
-----
Drug Alcohol Depend. 2004 Apr 9;74(1):61-70.
Efficacy of fluvoxamine in preventing relapse in alcohol
dependence: a one-year, double-blind, placebo-controlled multicentre study with
analysis by typology.
Chick J, Aschauer H, Hornik K; Investigators' Group.
Department of Psychiatry, Royal Edinburgh Hospital, University of Edinburgh,
Edinburgh EH10 5HF, Scotland, UK. j.chick@compuserve.com
Patients with a diagnosis of alcohol dependence, detoxified and abstinent for
10-30 days, were randomly allocated to placebo or the serotonin reuptake
inhibitor, fluvoxamine (up to 300 mg per day), plus counselling and support. In
the intention to treat sample of 493, there was a trend for the fluvoxamine
group to do worse than the placebo group on the primary outcome criteria:
abstinence; and relapse defined as drinking > or =5 units on an occasion and >
or =4 such occasions in a week, or > or =12 units on an occasion (1 unit = 9g
ethanol). When typology of alcoholism was assigned by scores on the
Tridimensional Personality Questionnaire, Types I and II had similar rates of
survival without relapse on placebo (PLC I: 19.3%, n = 135; PLC II: 18.2%, n =
110), but on fluvoxamine Type II did worse than Type I (FLU I: 13.7%, n = 131;
FLU II: 6.14%, n = 114) (P < 0.01). When typology was assigned on the basis of
age of onset of alcohol problems (< or = age 25, or > age 25), early-onset
patients in the fluvoxamine group relapsed more frequently than late-onset
patients in that group (no longer significant after adjustment for gender), as
did those who commenced regular drinking before age 25 (both with and without
adjustment for gender). One explanation for our finding could be that
impulsivity in early-onset or Type II patients may be accentuated by serotonin
enhancement.
-----
Drug Alcohol Depend. 2004 Apr 9;74(1):1-13.
A systematic review of the effectiveness of the community
reinforcement approach in alcohol, cocaine and opioid addiction.
Roozen HG, Boulogne JJ, van Tulder MW, van den Brink W, De Jong CA, Kerkhof AJ.
Department of Clinical Psychology, Vrije Universiteit Amsterdam, van der
Boechorststraat 1, 1081 BT Amsterdam, The Netherlands. hg.roozen@psy.vu.nl
The community reinforcement approach (CRA) has been applied in the treatment of
disorders resulting from alcohol, cocaine and opioid use. The objectives were to
review the effectiveness of (1) CRA compared with usual care, and (2) CRA versus
CRA plus contingency management. Studies were selected through a literature
search of RCTs focusing on substance abuse. The search yielded 11 studies of
mainly high methodological quality. The results of CRA, when compared to usual
care: there is strong evidence that CRA is more effective with regard to number
of drinking days, and conflicting evidence with regard to continuous abstinence
in the alcohol treatment. There is moderate evidence that CRA with disulfiram is
more effective in terms of number of drinking days, and limited evidence that
there is no difference in effect in terms of continuous abstinence. Furthermore,
there is strong evidence that CRA with "incentives" is more effective with
regard to cocaine abstinence. There is limited evidence that CRA with
"incentives" is more effective in an opioid detoxification program. There is
limited evidence that CRA is more effective in a methadone maintenance program.
Finally, there is strong evidence that CRA with abstinence-contingent
"incentives" is more effective than CRA (non-contingent incentives) treatment
aimed at cocaine abstinence.
-----
Ann Intern Med. 2004 Apr 6;140(7):557-68.
Behavioral counseling interventions in primary care to reduce
risky/harmful alcohol use by adults: a summary of the evidence for the U.S.
Preventive Services Task Force.
Whitlock EP, Polen MR, Green CA, Orleans T, Klein J; U.S. Preventive Services
Task Force.
Oregon Evidence-based Practice Center, Kaiser Permanente Center for Health
Research, and Oregon Health & Science University, Portland, Oregon 97227-1110,
USA.
BACKGROUND: Primary health care visits offer opportunities to identify and
intervene with risky or harmful drinkers to reduce alcohol consumption. PURPOSE:
To systematically review evidence for the efficacy of brief behavioral
counseling interventions in primary care settings to reduce risky and harmful
alcohol consumption. DATA SOURCES: Cochrane Database of Systematic Reviews,
Database of Research Effectiveness (DARE), MEDLINE, Cochrane Controlled Clinical
Trials, PsycINFO, HealthSTAR, CINAHL databases, bibliographies of reviews and
included trials from 1994 through April 2002; update search through February
2003. STUDY SELECTION: An inclusive search strategy (alcohol* or drink*)
identified English-language systematic reviews or trials of primary care
interventions to reduce risky/harmful alcohol use. Twelve controlled trials with
general adult patients met our quality and relevance inclusion criteria. DATA
EXTRACTION: Investigators abstracted study design and setting, participant
characteristics, screening and assessment procedures, intervention components,
alcohol consumption and other outcomes, and quality-related study details. DATA
SYNTHESIS: Six to 12 months after good-quality, brief, multicontact behavioral
counseling interventions (those with up to 15 minutes of initial contact and at
least 1 follow-up), participants reduced the average number of drinks per week
by 13% to 34% more than controls did, and the proportion of participants
drinking at moderate or safe levels was 10% to 19% greater compared with
controls. One study reported maintenance of improved drinking patterns for 48
months. CONCLUSIONS: Behavioral counseling interventions for risky/harmful
alcohol use among adult primary care patients could provide an effective
component of a public health approach to reducing risky/harmful alcohol use.
Future research should focus on implementation strategies to facilitate adoption
of these practices into routine health care.
-----
J Consult Clin Psychol. 2004 Apr;72(2):317-27.
Targeted naltrexone treatment moderates the relations between
mood and drinking behavior among problem drinkers.
Kranzler HR, Armeli S, Feinn R, Tennen H.
Alcohol Research Center, Department of Psychiatry, University of Connecticut
School of Medicine, Farmington, CT 06030-2103, USA. kranzler@psychiatry.uchc.edu
One hundred fifty-three problem drinkers were randomly assigned to receive
naltrexone 50 mg or placebo on a daily or targeted (to high-risk drinking
situations) basis. Using structured nightly diaries, participants recorded
negative and positive mood, desire to drink, and alcohol consumption over 8
weeks. Results indicated that individuals engaged in any drinking and heavy
drinking more on days characterized by relatively higher levels of positive or
negative mood states. Naltrexone attenuated the positive association between
heavy drinking and both positive and negative mood, and targeted administration
attenuated the positive association between heavy drinking and positive mood.
There was also evidence that desire to drink mediated the effect of targeted
administration on the relation between positive mood and any drinking that day.
These findings underscore the utility of daily measurement for understanding the
processes that underlie pharmacological interventions for problem drinking.
-----
JAMA. 2004 Apr 21;291(15):1887-96.
Treatment of depression in patients with alcohol or other drug
dependence: a meta-analysis.
Nunes EV, Levin FR.
Depression Evaluation Service, New York State Psychiatric Institute and
Department of Psychiatry, Columbia University, New York 10032, USA. nunesed@pi.cpmc.columbia.edu
CONTEXT: Depression and substance abuse are common and costly disorders that
frequently co-occur, but controversy about effective treatment for patients with
both disorders persists. OBJECTIVE: To conduct a systematic review and
meta-analysis to quantify the efficacy of antidepressant medications for
treatment of combined depression and substance use disorders. DATA SOURCES:
PubMed, MEDLINE, and Cochrane database search (1970-2003), using the keywords
antidepressant treatment or treatment depressed in conjunction with each of the
following alcohol dependence, benzodiazepine dependence, opiate dependence,
cocaine dependence, marijuana dependence, and methadone; a search of
bibliographies; and consultation with experts in the field. STUDY SELECTION:
Among inclusion criteria used for study selection were prospective, parallel
group, double-blind, controlled clinical trials with random assignment to an
antidepressant medication or placebo for which trial patients met standard
diagnostic criteria for current alcohol or other drug use and a current unipolar
depressive disorder. Of the more than 300 citations extracted, 44 were
placebo-controlled clinical trials, 14 of which were selected for this analysis
and included 848 patients: 5 studies of tricyclic antidepressants, 7 of
selective serotonin re-uptake inhibitors, and 2 from other classes DATA
EXTRACTION: We independently screened the titles and abstracts of each citation,
identified placebo-controlled trials of patients with both substance dependence
and depression, applied the inclusion criteria, and reached consensus. Data on
study methods, sample characteristics, and depression and substance use outcomes
were extracted. The principal measure of effect size was the standardized
difference between means on the Hamilton Depression Scale (HDS). DATA SYNTHESIS:
For the HDS score, the pooled effect size from the random-effects model was 0.38
(95% confidence interval, 0.18-0.58). Heterogeneity of effect on HDS across
studies was significant (P <.02), and studies with low placebo response showed
larger effects. Moderator analysis suggested that diagnostic methods and
concurrent psychosocial interventions influenced outcome. Studies with larger
depression effect sizes (>0.5) demonstrated favorable effects of medication on
measures of quantity of substance use, but rates of sustained abstinence were
low. CONCLUSIONS: Antidepressant medication exerts a modest beneficial effect
for patients with combined depressive- and substance-use disorders. It is not a
stand-alone treatment, and concurrent therapy directly targeting the addiction
is also indicated. More research is needed to understand variations in the
strength of the effect, but the data suggest that care be exercised in the
diagnosis of depression-either by observing depression to persist during at
least a brief period of abstinence or through efforts by clinical history to
screen out substance-related depressive symptoms.
-----
Alcohol Clin Exp Res. 2004 Mar;28(3):433-40.
Nefazodone treatment of comorbid alcohol dependence and major
depression.
Hernandez-Avila CA, Modesto-Lowe V, Feinn R, Kranzler HR.
Department of Psychiatry, University of Connecticut School of Medicine,
Farmington, Connecticut, USA.
BACKGROUND: Major depression is a common comorbid condition among individuals
with alcohol dependence. This study examined the effects of nefazodone, a
norepinephrine and serotonin reuptake blocker and 5-hydroxytryptamine-2 receptor
antagonist, on mood and anxiety symptoms and drinking behavior in a sample of
depressed alcoholics. METHODS: This study was a double-blind, placebo-controlled
comparison of nefazodone (200-600 mg/day) or placebo in a sample of
alcohol-dependent subjects (n = 41; 52% women) with current major depression.
After a 1-week placebo lead-in period, subjects were randomly assigned to
receive study medication and supportive psychotherapy for 10 weeks. RESULTS:
Depressive and anxiety symptoms declined significantly over time. Although the
nefazodone group showed greater reductions in these symptoms, the effects did
not reach statistical significance. Nonetheless, nefazodone-treated subjects
showed a significantly greater reduction in heavy drinking days and in total
drinks compared with placebo-treated subjects. CONCLUSIONS: The lack of
significant effects on depression and anxiety symptoms may reflect limited
statistical power. Despite the small sample size, nefazodone significantly
reduced some measures of alcohol consumption in this sample of depressed
alcoholics.
-----
J Psychopharmacol. 2004 Mar;18(1):88-93.
Mirtazapine improves alcohol detoxification.
Liappas J, Paparrigopoulos T, Malitas P, Tzavellas E, Christodoulou G.
Athens University Medical School, Department of Psychiatry, Eginition Hospital,
Athens, Greece. egslelabath@hol.gr
The objective of the present study was to determine whether a combined
psychotherapeutic-psychopharmacological (with mirtazapine) treatment of
collateral anxiety and depressive symptomatology during the post-withdrawal
phase of alcoholism facilitates the process of alcohol detoxification, which is
a decisive stage in the treatment of alcohol-dependent individuals. For that
purpose, the rate of remission of anxiety and depressive symptoms over a 4-week
detoxification period was evaluated between two groups: the first group followed
a standard detoxification protocol (n = 33) and the second group was assigned to
mirtazapine in addition to standard treatment (n= 35). A marked reduction of
anxiety and depressive symptoms was demonstrated in both groups. However,
patients on mirtazapine improved more and at a faster rate compared to controls.
Thus, mirtazapine, used adjunctively to short-term psychotherapy, may help the
detoxification process by minimizing physical and subjective discomfort.
Consequently, it may improve patient compliance in alcohol detoxification
programs and facilitate the initial phase treatment of alcohol abuse dependence.
-----
Alcohol Clin Exp Res. 2004 Feb;28(2):302-12.
Pharmacological treatment of alcohol abuse/dependence with
psychiatric comorbidity.
Le Fauve CE, Litten RZ, Randall CL, Moak DH, Salloum IM, Green AI.
Division of Clinical and Prevention Research, Treatment Research Branch, NIAAA,
Bethesda, Maryland, USA. clefauve@NIAAA.nih.gov
This article represents the proceedings of a symposium at the 2003 annual
meeting RSA in Fort Lauderdale, FL. It was organized and cochaired by Charlene
E. Le Fauve and Carrie L. Randall. The presentations were (1) Introduction, by
Charlene E. Le Fauve and Raye Z. Litten; (2) Treatment of co-occurring alcohol
use and anxiety disorders, by Carrie L. Randall and Sarah W. Book; (3)
Pharmacological treatment of alcohol dependent patients with comorbid
depression, by Darlene H. Moak; (4) Efficacy of valproate in bipolar alcoholics:
a double blind, placebo-controlled study, by Ihsan M. Salloum, Jack R.
Cornelius, Dennis C. Daley, Levent Kirisci, Johnathan Himmelhoch, and Michael E.
Thase; (5) Alcoholism and schizophrenia: effects of antipsychotics, by Alan I.
Green, Robert E. Drake, Suzannah V. Zimmet, Rael D. Strous, Melinda Salomon, and
Mark Brenner; and (6) Conclusions, by Charlene E. Le Fauve; discussant, Raye Z.
Litten. Alcohol-dependent individuals have exceptionally high rates of
co-occurring psychiatric disorders. Although this population is more likely to
seek alcoholism treatment than noncomorbid alcoholics, the prognosis for
treatment is often poor, particularly among patients with more severe
psychiatric illnesses. Development of effective interventions to treat this
population is in the early stages of research. Although the interaction between
the psychiatric condition and alcoholism is complex, progress has been made. The
NIAAA has supported a number of state-of-the-art pharmacological and behavioral
trials in a variety of comorbid psychiatric disorders. Some of these trials have
been completed and are presented here. The symposium presented some new research
findings from clinical studies with the aim of facilitating the development of
treatments that improve alcohol and psychiatric outcomes among individuals with
alcohol-use disorders and co-occurring psychiatric disorders. The panel focused
on social anxiety disorder, depression, bipolar disorder, and schizophrenia.
-----
Alcohol Clin Exp Res. 2004 Feb;28(2):295-301.
Development of novel pharmacotherapies for the treatment of
alcohol dependence: focus on antiepileptics.
Johnson BA, Swift RM, Ait-Daoud N, DiClemente CC, Javors MA, Malcolm RJ Jr.
Department of Psychiatry, University of Texas Health Science Center at San
Antonio, San Antonio, Texas 78229-3900, USA. bjohnson@uthscsa.edu
This article represents the proceedings of a symposium, "Development of Novel
Pharmacotherapies for the Treatment of Alcohol Dependence: Focus on
Antiepileptics," presented at the 2003 annual meeting of the Research Society on
Alcoholism in Fort Lauderdale, FL. The organizers and cochairs were Bankole A.
Johnson and Robert M. Swift. The presentations were (1) Development of
topiramate in the treatment of alcoholism, by Bankole A. Johnson; (2) Craving as
a predictor of treatment outcome in pharmacotherapy trials for the treatment of
alcoholism, by Nassima Ait-Daoud; (3) Use of biomarkers as a predictor of
treatment response in treating alcoholism, by Martin A. Javors; (4)
Psychotherapy to enhance compliance with pharmacotherapy in treatment trials for
alcohol dependence, by Carlo C. DiClemente; (5) Synopsis of promising
medications to treat alcoholism, by Robert M. Swift; and (6) New knowledge on
the development of antiepileptic medications for the treatment of alcoholism, by
Robert J. Malcolm, Jr.
-----
Alcohol Clin Exp Res. 2004 Jan;28(1):64-77.
Improvement in quality of life after treatment
for alcohol dependence with acamprosate and
psychosocial support.
Morgan MY, Landron F, Lehert P; For the New European Alcoholism
Treatment Study Group.
Centre for Hepatology, Royal Free Campus, Royal Free and University
College Medical School, University College London, London, United
Kingdom. mymorgan@rfc.ucl.ac.uk
BACKGROUND: The impact of disease on health-related quality
of life is now well recognized, as is the importance of this variable
as a measure of treatment efficacy. METHODS: Patients from five
European countries were enrolled in an open, multicenter, prospective
study designed to observe outcome in dependent drinkers treated
for 6 months with acamprosate and psychosocial support. Version
1 of the 36-item Short Form Health Profile (SF-36v1) questionnaire
was administered at inclusion and at 3 and 6 months. Responses
were described as handicaps compared with an appropriately matched,
healthy reference population. One-way fixed ANOVA and simultaneous
stepwise linear regression analysis were used to identify potential
predictors of quality of life at baseline and after treatment.
RESULTS: Baseline SF-36v1 data were obtained from 1216 patients
(mean age, 43 +/- 9 years; 77% male). Mean values for all SF-36v1
dimensions were significantly lower in the patient population
than in the normative reference population; the most important
deficits were observed in physical and emotional role limitations
and in social functioning. The most important predictors of baseline
quality of life were severity of alcohol dependence, employment
status, psychiatric history, quantity and frequency of alcohol
consumption, attendance at Alcoholics Anonymous, global alcohol
health status, age, gender, and education. SF-36v1 data were obtained
from 686 patients at 3 months and from 497 at 6 months. Significant
improvements were observed in all SF-36v1 dimensional and summary
scores after 3 months of treatment (p < 0.001); further marginal
improvements were observed between 3 and 6 months. The most important
predictors of quality of life following treatment were the SF-36v1
profile at baseline, followed by abstinence duration; patients
who completed the trial and remained abstinent throughout showed
the greatest improvement. CONCLUSIONS: Health-related quality
of life is severly impaired in dependent drinkers. Treatment with
acamprosate and psychosocial support, by promoting abstinence,
improves the quality of life profile to levels comparable to those
observed in healthy individuals.
-----
Alcohol Clin Exp Res. 2004 Jan;28(1):51-63.
The efficacy of acamprosate in the maintenance
of abstinence in alcohol-dependent individuals:
results of a meta-analysis.
Mann K, Lehert P, Morgan MY.
Department of Addictive Behavior and Addiction Medicine, Central
Institute of Mental Health, University of Heidelberg, Mannheim,
Germany.
BACKGROUND: A number of clinical trials have been undertaken
to determine the efficacy of acamprosate in the maintenance of
abstinence in alcohol-dependent individuals. However, the reported
differences in patient populations, treatment duration, and study
endpoints make comparisons difficult. An assessment of the efficacy
of treatment with acamprosate was, therefore, undertaken using
meta-analytical techniques. METHODS: All randomized, placebo-controlled
trials (RCTs) that fulfilled predetermined criteria were identified
using (1) a language unrestricted search of 10 electronic databases;
(2) a manual search of relevant journals, symposia, and conference
proceedings; (3) cross-referencing of all identified publications;
(4) personal communications with investigators; and (5) scrutiny
of Merck-Sante's internal reports of all European trials. Study
quality was assessed, independently, by three blinded workers.
Key outcome data were identified; some outcome variables were
recalculated to ensure consistency across trials. The primary
outcome measure was continuous abstinence at 6 months; abstinence
rates were determined by estimating Relative Benefit (RB). RESULTS:
A total of 19 published 1 unpublished RCTs were identified that
fulfilled the selection criteria; 3 were excluded because the
documentation available was insufficient to allow adequate assessment.
The remaining 17 studies, which included 4087 individuals, 53%
of whom received active drug, were of good quality and were otherwise
reasonably comparable. There was no evidence of publication bias.
Continuous abstinence rates at 6 months were significantly higher
in the acamprosate-treated patients (acamprosate, 36.1%; placebo,
23.4%; RB, 1.47; [95% confidence intervals (CI): 1.29-1.69]; p
< 0.001). This effect was observed independently of the method
used for assigning missing data. The effect sizes in abstinent
rates at 3, 6, and 12 months were 1.33, 1.50, and 1.95, respectively.
At 12 months, the overall pooled difference in success rates between
acamprosate and placebo was 13.3% (95% CI, 7.8-18.7%; number needed
to treat, 7.5). Acamprosate also had a modest but significant
beneficial effect on retention (6.01%; [95% CI, 2.90-8.82]; p
= 0.0106). CONCLUSION: Acamprosate has a significant beneficial
effect in enhancing abstinence in recently detoxified, alcohol-dependent
individuals.
-----
Subst Use Misuse. 2004 Jan;39(1):135-78.
Therapist rotation--a new element in the outpatient
treatment of alcoholism.
Krampe H, Wagner T, Kufner H, Jahn H, Stawicki S, Reinhold
J, Timner W, Kroner-Herwig B, Ehrenreich H.
Department of Psychiatry, Georg-August-University, Max-Planck-Institute
for Experimental Medicine, Gottingen, Germany.
For nine years, the so-called "therapist rotation"
has been a central part of OLITA, the Outpatient Longterm Intensive
Therapy for Alcoholics. Thus far, the participation of several
equally responsible therapists in the treatment of a patient has
rarely been seen as a specific therapeutic approach. The present
article analyzes the therapist rotation from a theoretical and
clinical perspective. Articles concerned with the therapeutic
alliance in the treatment of substance use disorders are reviewed.
Furthermore, the literature on multiple psychotherapy, which may
be seen as the precedent of the therapist rotation is surveyed.
Based on the efficacy of multiple psychotherapy and the importance
of the therapeutic alliance in the treatment of substance use
disorders, the present work discusses the therapist rotation as
an essential factor for the success of OLITA. It considers both
potential advantages and disadvantages for patients and therapists
and tries to identify conditions under which this approach appears
to promote therapeutic interactions. Finally, the implementation
of therapist rotation into OLITA is described, including the theoretical
background of the program itself and the treatment procedure.
New areas of application for the therapist rotation are discussed.
-----
Neuropsychopharmacology. 2003 Apr;28(4):755-64.
A clinical laboratory paradigm for evaluating
medication effects on alcohol consumption:
naltrexone and nalmefene.
Drobes DJ, Anton RF, Thomas SE, Voronin K.
Charleston Alcohol Research Center, Department of Psychiatry and
Behavioral Sciences, Medical University of South Carolina, USA.
drobesdj@moffitt.usf.edu
Opiate antagonist medications have been shown to improve alcoholism
treatment, but few human laboratory-based studies investigating
mechanisms for these effects have been conducted on alcohol dependent
persons. The present study was designed to determine the impact
of two opiate antagonists on alcohol consumption among nontreatment-seeking
alcoholics (n=125) and social drinkers (n=90). Participants were
randomly assigned to receive placebo, naltrexone (titrated to
50 mg/day), or nalmefene (titrated to 40 mg/day) for 8 days with
an alcohol laboratory session on the final day. Alcohol consumption
was monitored in the natural environment during the first 5 medication
days, and during a choice consumption paradigm following a standard
'priming' alcohol dose in a bar-laboratory setting. Social drinkers
consumed less alcohol than alcoholics during the prelab medication
period and the laboratory choice consumption paradigm, and they
attained lower blood alcohol levels than alcoholics following
the priming drink. Both opiate antagonist medications equally
reduced drinking amounts and frequency among alcoholics but not
social drinkers, relative to placebo, during natural environment
and bar-lab alcohol consumption evaluations. Greater medication
side effects, mostly mild in nature, were observed in participants
taking nalmefene. These findings demonstrate that both naltrexone
and nalmefene can lead to reductions in alcohol consumption among
alcoholics who are not attempting to reduce drinking. Similar
laboratory paradigms may offer substantial advantages for observing
these effects during evaluation of other medications as well.
-----
Recent Dev Alcohol. 2003;16:247-62.
The status of serotonin-selective pharmacotherapy
in the treatment of alcohol dependence.
Pettinati HM, Kranzler HR, Madaras J.
Center for the Study of Addictions, Department of Psychiatry,
University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
19104, USA.
Research performed during the past 20 years has shown that
serotonin (5-hydroxytryptamine; 5-HT) neurotransmission is related
to alcohol dependence. Both theoretical and empirical research
have supported the idea that alcohol dependence is a chronic disease
and that, in addition, biological vulnerabilities contribute to
the pathogenesis of alcohol dependence. Preclinical studies have
consistently demonstrated that there is a relationship between
5-HT function and alcohol consumption. Furthermore, there is evidence
building that lends support for the existence of distinct alcoholic
subtypes that may be differentiated by the type or complexity
of their 5-HT dysfunction. Beyond excessive drinking, behaviors
that are indicators of 5-HT dysregulation are depression, anxiety,
impulsiveness, and early-onset problem drinking. This chapter
will discuss the usefulness of 5-HT-selective pharmacotherapy
in treating alcohol dependence and will provide both historical
and current perspectives on its use.
-----
Recent Dev Alcohol. 2003;16:217-45.
Advances in the use of naltrexone: an integration
of preclinical and clinical findings.
O'Malley SS, Froehlich JC.
Yale University School of Medicine, New Haven, Connecticut 06519,
USA.
Both preclinical and clinical studies are critical in the development
of effective pharmacotherapeutic approaches for treating alcoholism.
Nowhere has this been more evident than in the development of
naltrexone for treating alcohol relapse. As studies continue on
the use of naltrexone for modifying alcohol intake, promising
avenues for continued work on maximizing the efficacy of naltrexone
for treating alcohol abuse and alcoholism are emerging. Recent
research suggests that naltrexone can influence key components
of alcohol dependence, including loss of control over the decision
to drink and the amount of alcohol consumed. Although not uniformly
positive, the majority of clinical trials supports the hypothesis
that naltrexone can reduce the urge to drink, increase the number
of days abstinent, and minimize the risk of relapse to heavy drinking.
Human laboratory and preclinical paradigms that have investigated
how naltrexone alters patterns of drinking suggest that naltrexone
treatment results in earlier cessation of drinking within a session.
In addition, preclinical data suggest that the amount of alcohol
consumed declines during subsequent sessions in the presence of
naltrexone. Based on this analysis, future clinical trials should
consider using analytic approaches that evaluate patterns of drinking
(e.g., multiple event analysis) rather than single events (e.g.,
survival analysis). Furthermore, behavioral interventions and
instructions can also be developed to take advantage of this effect.
Additional preclinical and clinical work is warranted to identify
dosing strategies that ensure adequate drug levels while reducing
the possibility of developing tolerance to naltrexone. Finally,
studies designed to identify the characteristics of drinking populations
that are responsive to naltrexone and studies investigating the
potential advantage of combining naltrexone with agents that alter
a number of neurotransmitter systems are exciting new avenues
of research. Ultimately, these lines for research promise to provide
critical information that can be used to maximize the efficacy
of naltrexone for treating alcoholism.
-----
Aten Primaria. 2003 Feb 28;31(3):146-53.
[Effectiveness of medical counseling for alcoholic
patients and patients with excessive alcohol consumption seen
in primary care]
[Article in Spanish]
Fernandez Garcia JA, Ruiz Moral R, Perula de Torres LA, Campos
Sanchez L, Lora Cerezo N, Martinez de la Iglesia J; Grupo de Cordobes
de Investigacion en Atencion Primaria (GCIAP).
Medico de Familia. Investigador principal. Unidad Docente de Medicina
de Familia y Comunitaria de Cordoba. Spain.
AIM: To determine the effectiveness of medical counseling for
alcohol abuse, when it is provided in primary care centers. DESIGN:
Quasi-experimental, open, multicenter before-after study.Setting.
14 primary care physician's practices (7 rural, 7 urban) in the
province of Cordoba (Spain). PARTICIPANTS: 306 patients of both
sexes, recruited with a case-finding strategy, who consumed >=35
(men) or >=21 (women) IU per week, or who had alcohol dependence
syndrome (ADS) (MALTS score O>=11). Interventions. All patients
were offered brief counseling to reduce drinking, and all were
followed to evaluate their status 3 months, 1 year and 2 years
later. MAIN MEASURES: The response variable was self-reported
alcohol consumption together with normal GGT values or confirmation
of alcohol consumption by a relative. The results were subjected
to intention-to-treat analysis. RESULTS: Of the 306 patients included
in the study, 95.1% were men and 78.4% had ADS. After 2 years
38.89% (95% CI, 32.2%-44.3%) had attained their treatment goal:
23.85% were in complete abstinence, and 15.0% consumed moderate
amounts of alcohol below the limit considered to indicate risk.
Starting excessive consumption at less than 16 years of age (odds
ratio [OR], 3.0885), living in a slum (OR, 3.2103), smoking (OR,
1.7187), and a positive CAGE test (OR, 1.9949) were associated
with failure of the intervention (P<.05). CONCLUSIONS: Counseling
provided by the family doctor was highly effective under the usual
conditions of general practice, both for patients with excessive
alcohol consumption and for patients with con ADS.
-----
Addiction. 2003 Mar;98(3):325-37.
Long-term influence of duration and intensity
of treatment on previously untreated individuals with alcohol
use disorders.
Moos RH, Moos BS.
Center for Health Care Evaluation, Department of Veterans Affairs
and Stanford University, Palo Alto, CA, USA. bmmos@stanford.edu
AIMS: This study examined the influence of the duration and
intensity of the first episode of treatment for previously untreated
individuals with alcohol use disorders on short-term and long-term
outcomes, and the effect of additional treatment and delayed treatment
on outcomes. DESIGN, SETTING, PARTICIPANTS: A sample of alcoholic
individuals (n = 473) was recruited at alcoholism information
and referral centers and detoxification units and was surveyed
at baseline and 1 year, 3 years and 8 years later. MEASUREMENTS:
At each contact point, participants completed an inventory that
assessed their treatment utilization since the last assessment
and their current alcohol-related, psychological and social problems.
FINDINGS: Compared with individuals who remained untreated, individuals
who entered treatment relatively quickly and who obtained a longer
duration of treatment had better short- and long-term alcohol-related
outcomes and better short-term social functioning. Individuals
who obtained a longer duration of additional treatment had better
alcohol-related outcomes than individuals who obtained no additional
treatment but, among individuals who delayed treatment entry,
the duration of treatment was not associated with treatment outcomes.
In general, the intensity of treatment was not related to better
outcomes. CONCLUSIONS: Rapid entry into treatment and the duration
of treatment for alcohol use disorders may be more important than
the intensity of treatment. Treatment providers should consider
structuring their programs to emphasize continuity, rather than
intensity of care.
-----
J Consult Clin Psychol. 2003 Feb;71(1):118-28.
Coping skills and treatment outcomes in cognitive-behavioral
and interactional group therapy
for alcoholism.
Litt MD, Kadden RM, Cooney NL, Kabela E.
Department of Behavioral Sciences and Community Health, University
of Connecticut Health Center, Farmington 06030, USA. Litt@nso.uchc.edu
In the present study 128 alcohol dependent men and women received
26 weeks of group treatment in one of two modalities: Cognitive-behavioral
treatment (CBT) intended specifically to develop coping skills
or interactional therapy intended to examine interpersonal relationships.
Coping skills and drinking were assessed prior to and after treatment
and up to 18 months after intake. Results indicated that both
treatments yielded very good drinking outcomes throughout the
follow-up period. Increased coping skills was a significant predictor
of outcome. However, neither treatment effected greater increases
in coping than the other. Specific coping-skills training was
not essential for increasing the use of coping skills. The results
raise questions about the efficacy of specific treatment elements
of CBT in treatment of alcohol dependence.
-----
Eur Addict Res. 2003 Jan;9(1):1-7.
Symptom-triggered versus standard chlormethiazole
treatment of inpatient alcohol withdrawal: clinical implications
from a chart analysis.
Lange-Asschenfeldt C, Muller MJ, Szegedi A, Anghelescu I, Klawe
C, Wetzel H.
Department of Psychiatry, University of Mainz, Mainz, Germany.
lange@medscape.com
To evaluate clinical effectiveness and safety of 2 different
detoxification treatment protocols, a chart analysis of hospital
inpatients consecutively admitted for alcohol withdrawal during
one year was undertaken. Records of 33 patients receiving symptom-triggered
treatment (using a modified version of the revised Clinical Institute
Withdrawal Assessment for Alcohol Scale) were compared with those
of patients treated by applying a fixed-dose regimen (n = 32).
Patients (45.3 +/- 9.8 years, 21% female) of both groups were
comparable regarding illness severity, epidemiologic parameters
as well as complications during the observed treatment period.
Under symptom-triggered therapy, chlormethiazole (CMZ) treatment
duration (4.2 +/- 3.5 vs. 7.5 +/- 3.3 days, Mann-Whitney U test:
p = 0.0003) and cumulative CMZ dosage (4352 +/- 4589 vs. 9921
+/- 6599 mg, Mann-Whitney U test: p = 0.0004) were significantly
reduced. The daily CMZ dose was significantly lower at days 1-5
in the group receiving symptom-triggered treatment. There was
no influence of age on the outcome parameters of either treatment
group. In conclusion, an individualized symptom-triggered treatment
of alcohol withdrawal with CMZ seems to be equally safe but more
efficient than a scheduled regimen. Copyright 2003 S. Karger AG,
Basel
-----
Arch Gen Psychiatry. 2003 Jan;60(1):92-9.
Comparing and combining naltrexone and acamprosate
in relapse prevention of alcoholism: a double-blind, placebo-controlled
study.
Kiefer F, Jahn H, Tarnaske T, Helwig H, Briken P, Holzbach R,
Kampf P, Stracke R, Baehr M, Naber D, Wiedemann K.
Department of Psychiatry, University Hospital of Hamburg, Martinistr
52, D-20246 Hamburg, Germany. kiefer@psyunihh.de
BACKGROUND: Naltrexone and acamprosate have been shown to be
effective in relapse prevention of alcoholism via different pharmacologic
mechanisms. Since it remains uncertain whether both substances
are equally efficient and whether a combination of both drugs
potentiates the efficacy, we conducted the first published controlled
study comparing and combining both compounds. METHODS: After detoxification,
160 patients with alcoholism participated in a randomized, double-blind,
placebo-controlled protocol. Patients received naltrexone, acamprosate,
naltrexone plus acamprosate, or placebo for 12 weeks. Patients
were assessed weekly by interview, self-report, questionnaires,
and laboratory screening. Time to first drink, time to relapse,
and the cumulative abstinence time were the primary outcome measures.
RESULTS: Naltrexone, acamprosate, and the combined medication
were significantly more effective than placebo. Comparing the
course of nonrelapse rates between naltrexone and acamprosate,
the naltrexone group showed a tendency for a better outcome regarding
time to first drink and time to relapse. The combined medication
was most effective with significantly lower relapse rates than
placebo and acamprosate but not naltrexone. CONCLUSIONS: The results
of this study support the efficacy of pharmacotherapeutic strategies
in the relapse prevention of alcoholism. Naltrexone and acamprosate,
especially in combination, considerably enhance the potential
of relapse prevention.
-----
Alcohol Clin Exp Res. 2002 Dec;26(12):1816-22.
Long-term effects of and physiological responses
to nitrous oxide gas treatment during alcohol withdrawal: a double-blind,
placebo-controlled trial.
Alho H, Methuen T, Paloheimo M, Strid N, Seppa K, Tiainen J, Salaspuro
M, Roine R.
National Public Health Institute, Department of Mental Health
and Alcohol Research, Helsinki, Finland. hannu.alho@ktl.fi
BACKGROUND: Nitrous oxide gas (N2O) has been proposed to be
effective in the treatment of the alcohol withdrawal syndrome
(AWS). This has not been proved, however, in studies performed
according to good clinical practice guidelines. Moreover, previous
studies have not measured end tidal N2O concentrations or physiologic
responses during N2O treatment. We have recently reported that
in a double-blind, randomized, controlled setting, N2O was not
superior to placebo in relieving AWS symptoms. In this previous
study, we did not find significant differences between the treatments
either in the Clinical Institute Withdrawal Assessment of Alcohol
scores or in the total use of benzodiazepines (diazepam and temazepam).
The aim of the present study was to characterize other effects
and side effects of the N2O treatment using several objective
measures and to study the possible long-term efficacy of the treatment.
METHODS: A total of 105 inpatients who had AWS and were admitted
to the A-Clinic detoxification center were included in the study.
The subjects were randomly assigned to one of the following three
treatments: (1) N2O/oxygen (from 30 to 70% in oxygen), (2) air/oxygen
(30%/70%), and (3) medical (normal) air. During the single 45-min
treatment period, end-tidal N2O, carbon dioxide, and oxygen concentrations
were measured. The physiologic responses were studied by measuring
heart rate, blood pressure, pulse oximetric saturation, frontal
muscle electromyographic activity, and plethysmographic pulse
amplitude. Long-term effects were studied by measuring craving
with the Obsessive-Compulsive Drinking Scale; severity of dependency
with Severity of Alcohol Dependence Data; and liver enzymes with
aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyltransferase
3 and 6 months after the treatment. RESULTS: Patients in the N2O
group demonstrated significantly higher facial muscle electromyographic
activity and higher pulse amplitude than the air-treated subjects.
Self-reported side effects between the gas treatments, however,
did not differ between the groups. Regarding long-term effects
of the treatments, there were no differences between the groups.
CONCLUSIONS: Contrary to previously published data, N2O treatment
did not decrease craving or liver enzymes during the 6-month follow-up.
At the concentration used, N2O treatment produced signs of arousal
instead of strong sedation.
-----
J Clin Psychopharmacol. 2002 Dec;22(6):592-8.
Lack of efficacy of naltrexone in the prevention
of alcohol relapse: results from a
German multicenter study.
Gastpar M, Bonnet U, Boning J, Mann K, Schmidt LG, Soyka M, Wetterling
T, Kielstein V, Labriola D, Croop R.
Department of Psychiatry of the University of Essen, Germany.
markus.gastpar@uni-essen.de
In a placebo-controlled, double-blind German multicenter study
(seven sites) the efficacy of naltrexone as an adjunctive treatment
in alcoholism to maintain abstinence was assessed for 12 weeks.
A total of 171 detoxified patients (97.7% met the DSM-III-R criteria
for alcohol dependence) were included. Patients had been abstinent
for a mean of 19.5 +/- 9.4 days at study entry. Eighty-four and
87 patients were randomized to receive naltrexone (50 mg/day)
and placebo, respectively. Each site was instructed to provide
its usual psychosocial alcohol treatment program. The primary
effectiveness measure was the time to first heavy drinking as
derived from self-reports of drinking (timeline-follow-back method).
Secondary effectiveness measures included time to first drink,
amount of alcohol consumption, intensity of craving, severity
of alcoholism problems, and liver enzymes. Thirty-three (38%)
placebo patients and 28 (33%) naltrexone patients discontinued
the study. At endpoint, 62% of the patients in each group did
not have an episode of heavy drinking. Also, there were no significant
differences between the study groups concerning secondary effectiveness
measures as well as compliance and adverse clinical events--with
the exception of the gamma-GT, which was significantly greater
reduced in the naltrexone group throughout the study. Based upon
an intention-to-treat population, this study confirms the safety
but not the efficacy of naltrexone in prevention of alcohol relapse.
Nevertheless, the question arises whether self-reports of drinking
are more reliable than gamma-GT as a measure of recent alcohol
consumption.
-----
Eur Arch Psychiatry Clin Neurosci. 2002 Oct;252(5):197-200.
A combination of carbamazepine/tiapride in outpatient
alcohol detoxification.
Results from an open clinical study.
Soyka M, Morhart-Klute V, Horak M.
Psychiatric Hospital, University of Munich, Nussbaumstr 7, 80336
Munchen, Germany.
This was an open, prospective study to examine the efficacy,
practicability and medical safety of a combination of carbamazepine
and tiapride in outpatient detoxification of alcohol-dependent
patients. Patients were carefully screened for relevant neuropsychiatric
disorders and then seen on a daily outpatient basis. Patients
received medication if the initial CIWA-A score exceeded 16 points.
Fifty consecutively admitted patients entered the program; 49
(98 %) successfully ended treatment. The mean initial dose for
carbamazepine was 628 mg or 332 mg for tiapride. No serious medical
complications or adverse events were observed. In general, medication
was well tolerated. Withdrawal symptomatology as indicated by
CIWA-A scores clearly decreased over time. Most frequently named
side effects were sedation (63 %), hyperhidrosis (49 %), lack
of drive (38 %), dry mouth (31 %) and orthostatic dysregulation
or vertigo (22 %). Results from this study suggest that a combination
of the anticonvulsant carbamazepine and tiapride is an effective
and safe treatment for outpatient alcohol detoxification in patients
with moderate severity of withdrawal syndrome.
-----
Subst Abus. 2002 Sep;23(3):171-82.
Cognitive variables in alcohol dependent patients
with elevated depressive symptoms: changes and predictive utility
as a function of treatment modality.
Ramsey SE, Brown RA, Stuart GL, Burgess ES, Miller IW.
Department of Psychiatry and Human Behavior, Brown University
School of Medicine, Providence, Rhode Island 02903, USA. susan_ramsey@brown.edu
The aim of the current study was to examine, through posthoc
analyses, changes in and predictive utility of mood-related cognitive
variables as a function of treatment modality in a group of alcohol
dependent patients with elevated depressive symptoms. In addition
to the background partial hospital treatment for alcoholism which
lasted a mean of 21.2 days, study patients (n = 35) received cognitive-behavioral
treatment for depression (CBT-D) or a control treatment consisting
of relaxation training (RTC). While both groups showed improvement
on dysfunctional attitudes during treatment, only the CBT-D group
improved on measures of alcohol-related expectancies. Changes
in cognitive variables during treatment predicted drinking outcomes,
and the predictors of drinking outcomes varied across the two
treatments. Among the RTC patients, changes in positive alcohol-related
expectancies were negatively correlated with drinking frequency
and quantity at follow-up. However, for the CBT-D patients, changes
in self-efficacy concerning negative mood situations and negative
alcohol-related expectancies were negatively correlated with drinking
at longer-term follow-up. The results of this study provide evidence
concerning the mechanisms by which the treatment modalities examined
may affect patient outcome. Although these results are preliminary
in nature, they do suggest that future research might examine
efforts to capitalize on these mechanisms through the facilitation
of changes found to predict better drinking outcomes in this study.
-----
Health Bull (Edinb). 2002 Jan;60(1):55-61.
Missed opportunities? Management of patients with
alcohol problems in a surgical ward.
Aarvold A, Crofts T.
Department of Surgery, Royal Infirmary of Edinburgh, Lauriston
Place, Edinburgh.
Patients with alcohol problems necessitate treatment with counselling,
and hospital admission for alcohol related complaints presents
an ideal opportunity for this. This paper aims to examine the
management of patients with alcohol related complaints on a surgical
ward. Patients were interviewed to analyse the extent of their
alcohol problem and counselling received, and doctors completed
a questionnaire about counselling they offered. Forty seven out
of 435 patients (10.8%) had alcohol related complaints; 28 of
these 47 were alcohol dependent; 22 out of 28 alcohol dependent
patients were not spoken to about their alcohol consumption on
this admission. Thirteen doctors responsible for hospital admissions
completed the questionnaire: although an alcohol history was almost
always taken, counselling was rarely offered. In conclusion, the
management of patients with alcohol problems in the emergency
admission was sub-optimal. The treatment most needed was counselling,
and this ideal opportunity for intervention was almost always
missed.
-----
Am J Geriatr Psychiatry. 2002 Nov-Dec;10(6):740-7.
Alcoholism treatment adherence: older age predicts
better adherence and drinking outcomes.
Oslin DW, Pettinati H, Volpicelli JR.
Section of Geriatric Psychiatry, Department of Psychiatry, University
of Pennsylvania, Philadelphia 19104, USA. oslin@mail.med.upenn.edu
OBJECTIVE: Adherence to treatment has been demonstrated to
be an important factor for remission from alcohol dependence.
The authors compared therapy and medication adherence for treatment
of alcohol dependence in older adults with adherence in younger
adults. METHODS: All subjects were participants in a randomized,
double-blind, placebo-controlled efficacy trial of naltrexone
for the treatment of alcohol dependence. All subjects received
a medically-based psychosocial intervention focused on motivating
patients to change and on adherence to treatment. The therapy
is nonconfrontational and is delivered by a nurse-practitioner.
RESULTS: Compared with younger adults, older adults had greater
attendance at therapy sessions and greater adherence to the medication.
Age-group was the only pretreatment factor associated with adherence.
The greater adherence in older adults translated to less relapse
than in younger adults. CONCLUSION: Treatment for alcohol dependence
can be effective for older adults. Older adults appear to respond
well to a medically-oriented program that is supportive and individualized.
In fact, findings from this study suggest that older adults can
be treated in mixed-age treatment settings when psychotherapeutic
strategies are used that are age-appropriate and delivered on
an individual basis.
-----
Can J Clin Pharmacol. 2002 Fall;9(3):130-6.
Naltrexone in the treatment of alcohol dependence:
a Canadian trial.
Romach MK, Sellers EM, Somer GR, Landry M, Cunningham GM, Jovey
RD, McKay C, Boislard J, Mercier C, Pepin JM, Perreault J, Lemire
E, Baker RP, Campbell W, Ryan D.
Department of Psychiatry, University of Toronto. myroslava.romach@utoronto.ca
OBJECTIVES: Alcohol dependence is a prevalent psychiatric disorder
affecting approximately 12% of the adult population at some point
in their lifetime. Psychosocial treatments are associated with
only modest success rates. The first Canadian clinical trial with
naltrexone, an opiate antagonist, was conducted to evaluate its
safety and usefulness as an adjunctive treatment in the management
of alcohol dependence. METHODS: One hundred twenty alcohol-dependent
individuals were assessed to receive treatment with 50 mg of naltrexone
orally for 12 weeks in an open-label trial. Patients were seen
biweekly and received a concurrent psychosocial intervention.
Treatment was conducted at multiple sites in Canada. RESULTS:
Fifty-four per cent of subjects completed the entire 12 weeks
of treatment. During the study, 39% of patients abstained, while
of the individuals reporting drinking at baseline, 86% were consuming
less alcohol by their final visit. These reductions were accompanied
by a significant decrease in craving for alcohol at week 12, as
measured by the Obsessive Compulsive Drinking Scale (P<0.01).
Naltrexone was well tolerated and no serious adverse events were
experienced. CONCLUSIONS: The data lend support to the hypothesis
that endogenous opioid activity is involved in the regulation
of alcohol intake, and that antagonists of endogenous opioids
decrease craving and drinking. Opiate antagonists such as naltrexone
are a new strategy in the treatment of alcohol dependence. Naltrexone
can be safely given to female and male alcoholics, is acceptable
to patients, and plays a role in reducing alcohol consumption
and preventing relapse to heavy drinking.
-----
Alcohol Clin Exp Res. 2002 Oct;26(10):1545-52.
Amisulpride does not prevent relapse in primary
alcohol dependence: results of a pilot randomized, placebo-controlled
trial.
Marra D, Warot D, Berlin I, Hispard E, Notides C, Tilikete S,
Payan C, Lepine JP, Dally S, Aubin HJ.
Department of Pharmacology and Psychiatry, Hospital Pritie-Salpetriere,
Paris, France. donata.marra@psl.ap-hop-paris.fr
BACKGROUND: Few medications have been proved to be effective
in preventing relapse in alcoholism. The mesolimbic dopamine system
is known to play an important role in alcohol dependence. Amisulpride,
a substituted benzamide, seems to facilitate dopaminergic neurotransmission
at low doses. METHODS: After short-term, inpatient detoxification,
71 patients participated in a randomized, double-blind, placebo-controlled
study to evaluate the efficacy of amisulpride in relapse prevention.
Patients received amisulpride 50 mg/day or placebo for 6 months.
RESULTS: There were no differences between the two groups of treatment
for time to first drink, length of time before dropout, number
of drinking days, and number of heavy drinking days. However,
significantly more patients who were treated with amisulpride
than those who were treated with placebo were nonabstinent and
had relapsed at each visit. Craving for alcohol was significantly
higher in the amisulpride than in the placebo group. Transaminases,
gamma-glutamyl-transferase, and mean erythrocyte corpuscular volume
were regularly higher in the amisulpride group than in the placebo
group. CONCLUSIONS: The results indicate that treatment with amisulpride
was not effective in preventing relapse to drinking in detoxified,
alcohol-dependent patients. The significance of this finding is
discussed, particularly in terms of the effects of neuroleptics
on alcohol consumption.
-----
Alcohol Clin Exp Res. 2002 Oct;26(10):1529-38.
The European NEAT program: an integrated approach
using acamprosate and psychosocial support for the prevention
of relapse in alcohol-dependent patients with a statistical modeling
of therapy success prediction.
Pelc I, Ansoms C, Lehert P, Fischer F, Fuchs WJ, Landron F, Pires
Preto AJ, Morgan MY.
Hospital Universitaire Brugmann, Bruxelles, Belgium.
BACKGROUND: A multicenter, prospective study was conducted
in five European countries to observe outcome in alcohol misusers
treated for 24 weeks with acamprosate and various psychosocial
support techniques, within the setting of standard patient care.
METHODS: Patients diagnosed as alcohol dependent using DSM-III-R
criteria were treated, for 24 weeks, with acamprosate and appropriate
psychosocial support. Potential predictor variables were recorded
at inclusion. Drinking behavior was monitored throughout; the
proportion of cumulative abstinence days was the principal outcome
measure. The influence of baseline clinical and demographic variables
on outcome was assessed using multiple regression analysis. Adverse
events were recorded systematically. RESULTS: A total of 1289
patients were recruited; 1230 took at least one dose of the drug
and provided at least one set of follow-up data; 543 (42.1%)patients
were observed for the full 24-week period. The overall proportion
of cumulative abstinence days was 0.48. Multiple physical and
psychiatric comorbidities and a history of drug addiction were
negatively correlated with outcome, as were, to a lesser extent,
multiple previous episodes of detoxification, unemployment, and
living alone. Older age and stable employment were positively
associated with outcome. The difference in the unadjusted proportion
of cumulative abstinence days between countries was significant
( < 0.001) but less so when adjusted for the predictive factors
identified in the multivariate model ( < 0.019). Overall, outcome
was not influenced by the nature of the psychosocial support provided.
Adverse events were generally mild, with gastrointestinal disorders,
which occurred in 21.5% of patients, being the most frequent.
CONCLUSIONS: This open-label study confirms the efficacy and safety
of acamprosate in the treatment of alcohol dependence in the setting
of standard patient care. Treatment benefit was observed irrespective
of the nature of the psychosocial support provided. Predictors
of the response to treatment were identified; their heterogeneous
distribution within the study population explained, at least in
part, the differences in outcome between countries.
-----
Neuropsychopharmacology. 2002 Oct;27(4):596-606.
A pharmacokinetic and pharmacodynamic drug interaction
study of acamprosate and naltrexone.
Mason BJ, Goodman AM, Dixon RM, Hameed MH, Hulot T, Wesnes K,
Hunter JA, Boyeson MG.
Division of Substance Abuse, Department of Psychiatry and Behavioral
Sciences, University of Miami School of Medicine, Miami, FL, USA.
bjmason246@aol.com
Acamprosate and naltrexone have each demonstrated safety and
efficacy for alcohol dependence in placebo-controlled clinical
trials. There is scientific and clinical interest in evaluating
these drugs in combination, given their high tolerability, moderate
effect sizes, different pharmacological profiles and potentially
different effects on drinking outcomes. Thus, this is the first
human pharmacokinetic and pharmacodynamic drug interaction study
of acamprosate and naltrexone. Twenty-four normal, healthy adult
volunteers participated in a double-blind, multiple dose, within
subjects, randomized, 3-way crossover drug interaction study of
the standard therapeutic dose of acamprosate (2 g/d) and the standard
therapeutic dose of naltrexone (50 mg/d), given alone and in combination,
with seven days per treatment condition and seven days washout
between treatments. Blood samples were collected on a standardized
schedule for pharmacokinetic analysis of naltrexone, 6-beta-naltrexol,
and acamprosate. A computerized assessment system evaluated potential
drug effects on cognitive functioning. Coadministration of acamprosate
with naltrexone significantly increased the rate and extent of
absorption of acamprosate, as indicated by an average 33% increase
in acamprosate maximum plasma concentration, 33% reduction in
time to maximum plasma concentration, and 25% increase in area
under the plasma concentration-time curve. Acamprosate did not
affect the pharmacokinetic parameters of naltrexone or 6-beta-naltrexol.
A complete absence of negative interactions on measures of safety
and cognitive function supports the absence of a contraindication
to co-administration of acamprosate and naltrexone in clinical
practice.
-----
Alcohol Clin Exp Res. 2002 Sep;26(9):1381-7.
A double-blind, placebo-controlled study of naltrexone
in the treatment of alcohol-dependence disorder: results from
a multicenter clinical trial.
Guardia J, Caso C, Arias F, Gual A, Sanahuja J, Ramirez M, Mengual
I, Gonzalvo B, Segura L, Trujols J, Casas M.
Department of Psychiatry, Addictive Behavior Unit, Hospital de
la Santa Creu i Sant Pau, Barcelona, Spain. jguardia@hsp.santapau.es
BACKGROUND: A 12-week, multicenter, double-blind, randomized,
parallel-group clinical trial to compare naltrexone and placebo
was carried out to determine the efficacy, safety, and tolerability
of naltrexone together with a psychosocial intervention in the
treatment of alcoholism. METHODS: A total of 202 alcohol-dependent
patients were assigned to 12 weeks' treatment with either naltrexone
or placebo. The relapse rate was evaluated by means of intention-to-treat
analyses. Alcohol consumption, craving, adverse events, and changes
in the biochemical markers of heavy drinking and possible toxicity
were evaluated in the 192 patients who were considered to be assessable.
RESULTS: The survival function for patients who were treated with
naltrexone was significantly better than that of the patients
who were treated with placebo (Kaplan-Meier log rank = 4, df =
1, p < 0.05). In addition, 7.9% of patients who were treated
with naltrexone relapsed as compared with 18.8% of those who received
placebo [chi = 5.89, df = 2, p = 0.050]. In comparing naltrexone
with placebo-treated patients, the most common adverse events
were abdominal pain [8.6% vs. 1%; (chi = 6.1, df = 1, p < 0.05)]
and headache [7.5% vs. 1% (chi = 5.1, df = 1, p < 0.05)]. CONCLUSIONS:
Naltrexone was well-tolerated, as the rate of adverse events was
low, and safe, as it did not interfere with the normalization
of biochemical markers of heavy drinking or alter liver function
markers. Naltrexone seemed to reduce relapse rate to heavy drinking,
but we found no differences in other alcohol consumption variables
between naltrexone- and placebo-treated groups. Although the naltrexone
group showed a tendency to consume fewer drinks per drinking day
and had a longer time to first drink, differences were not statistically
significant.
-----
Exp Clin Psychopharmacol. 2002 Aug;10(3):213-27.
Clinical uses of naltrexone: a review of the evidence.
Modesto-Lowe V, Van Kirk J.
Alcohol Research Center, Department of Psychiatry, University
of Connecticut School of Medicine, Farmington 06030-2103, USA.
modesto@neuron.uchc.edu
The implication of the opioidergic system in the pathogenesis
of various substance use disorders has led to renewed interest
in expanding the clinical uses of naltrexone, an opioid antagonist.
This article examines the evidence for the efficacy of naltrexone
in a variety of substance use and psychiatric disorders. Naltrexone
can be an effective treatment for alcohol and opioid dependence
if issues of compliance are adequately addressed. Thus far, no
definitive role has been found for naltrexone in the treatment
of other psychiatric disorders. Further research needs to be done
in self-injurious behavior, gambling, cocaine, and nicotine dependence.
-----
Aust N Z J Psychiatry. 2002 Oct;36(5):622-8.
Cognitive behavioural therapy combined with the
relapse-prevention medication acamprosate: are short-term treatment
outcomes for alcohol dependence improved?
Feeney GF, Young RM, Connor JP, Tucker J, McPherson A.
Department of Psychiatry, University of Queensland, Brisbane,
Australia. Gerald_Feeney@health.qld.gov.au
OBJECTIVE: The relapse prevention medication acamprosate has
been recently introduced to the Australian Pharmaceutical Benefits
Scheme (PBS) for the treatment of alcohol dependence. Overseas
clinical trials have demonstrated the efficacy of using acamprosate
as an adjunct to existing psychotherapeutic approaches. Research
has not examined treatment outcomes using a standardized clinical
approach. The objective of this study is to investigate the impact
of adding acamprosate to an established abstinence-based outpatient
alcohol rehabilitation programme in an Australian population.
METHODS: Fifty patients participated in an established 12-week,
outpatient, "contract" based Cognitive Behavioural Therapy
(CBT) alcohol abstinence programme and received acamprosate (CBT
+ acamprosate). Patients weighing > or = 60 kg were prescribed
acamprosate calcium 333 mg tablets, two tablets three times daily
(1998 mg/day) and those weighing < 60 kg received four tablets
(1332 mg/day) daily. Outcomes were compared with 50 historical,
matched controls, all of whom participated in the same program
without a relapse prevention medication (CBT alone). All patients
met DSM-IV criteria for alcohol dependence and the majority were
socially disadvantaged. RESULTS: Programme attendance across the
eight treatment sessions was similar in both the CBT + acamprosate
and the CBT alone conditions (P = 0.268). Relapse to alcohol use
occurred sooner and more frequently in the CBT alone group (P
= < 0.0005). Rehabilitation programme completion at 12 weeks
was 42% (CBT + acamprosate) compared with 32% for (CBT alone)
(P = < 0.204). Alcohol abstinence at 12 weeks was 38% (CBT
+ acamprosate) compared with 14% (CBT alone) (P = < 0.006).
CONCLUSION: Even within an alcohol dependent population characterized
by poor prognostic indices, the addition of acamprosate to an
established CBT outpatient programme significantly improved abstinence
rates over a 12-week period. The use of acamprosate as an adjunctive
treatment for alcohol dependence should be encouraged in Australia.
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Alcohol Alcohol. 2002 Sep-Oct;37(5):504-8.
Baclofen efficacy in reducing alcohol craving
and intake: a preliminary double-blind randomized
controlled study.
Addolorato G, Caputo F, Capristo E, Domenicali M, Bernardi M,
Janiri L, Agabio R, Colombo G, Gessa GL, Gasbarrini G.
Institute of Internal Medicine and Institute of Psychiatry, Catholic
University of Rome, Rome, Italy.
AIMS: The gamma-aminobutyric acid (GABA(B)) receptor agonist,
baclofen, has recently been shown to reduce alcohol intake in
alcohol-preferring rats and alcohol consumption and craving for
alcohol in an open study in humans. The present study was aimed
at providing a first evaluation of the efficacy of baclofen in
inducing and maintaining abstinence and reducing craving for alcohol
in alcohol-dependent patients in a double-blind placebo-controlled
design. METHODS: A total of 39 alcohol-dependent patients were
consecutively enrolled in the study. After 12-24 h of abstinence
from alcohol, patients were randomly divided into two groups.
Twenty patients were treated with baclofen and 19 with placebo.
Drug and placebo were orally administered for 30 consecutive days.
Baclofen was administered at the dose of 15 mg/day for the first
3 days and 30 mg/day for the subsequent 27 days, divided into
three daily doses. Patients were monitored as out-patients on
a weekly basis. At each visit alcohol intake, abstinence from
alcohol, alcohol craving and changes in affective disorders were
evaluated. RESULTS: A higher percentage of subjects totally abstinent
from alcohol and a higher number of cumulative abstinence days
throughout the study period were found in the baclofen, compared
to the placebo, group. A decrease in the obsessive and compulsive
components of craving was found in the baclofen compared to the
placebo group; likewise, alcohol intake was reduced in the baclofen
group. A decrease in state anxiety was found in the baclofen compared
to the placebo group. No significant difference was found between
the two groups in terms of current depressive symptoms. Baclofen
proved to be easily manageable and no patient discontinued treatment
due to the presence of side-effects. No patient was affected by
craving for the drug and/or drug abuse. CONCLUSIONS: Baclofen
proved to be effective in inducing abstinence from alcohol and
reducing alcohol craving and consumption in alcoholics. With the
limits posed by the small number of subjects involved, the results
of this preliminary double-blind study suggest that baclofen may
represent a potentially useful drug in the treatment of alcohol-dependent
patients and thus merits further investigations.
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Acta Psychiatr Scand. 2002 Sep;106(3):227-32.
Out-patient behaviour therapy in alcoholism: treatment
outcome after 2 years.
Burtscheidt W, Wolwer W, Schwarz R, Strauss W, Gaebel W.
Department of Psychiatry and Psychotherapy, Heinrich Heine University,
Duesseldorf, Germany. burtsche@uni-duesseldorf.de
OBJECTIVE: The main aim of the study was the evaluation of
out-patient behavioural approaches in alcohol dependence. Additionally,
the persistence of treatment effects and the impact of psychiatric
comorbidity in long-term follow-up was examined. METHOD: A total
of 120 patients were randomly assigned to non-specific supportive
therapy or to two different behavioural therapy programmes (coping
skills training and cognitive therapy) each comprising 26 weekly
sessions; the follow-up period lasted 2 years. RESULTS: Patients
undergoing behavioural therapy showed a consistent trend towards
higher abstinence rates; significant differences between the two
behavioural strategies could not be established. Moreover, the
results indicate a reduced ability of cognitive impaired patients
to cope with short-time abstinence violations and at a reduced
benefit from behavioural techniques for patients with severe personality
disorders. CONCLUSION: Behavioural treatment yielded long-lasting
effects and met high acceptance; yet, still in need of improvement
is the development of specific programmes for high-risk patients.
Copyright Blackwell Munksgaard 2002.
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Drug Alcohol Depend. 2002 Aug 1;67(3):323-30.
The use of divalproex in alcohol relapse prevention:
a pilot study.
Brady KT, Myrick H, Henderson S, Coffey SF.
Institute of Psychiatry and Behavioral Science, Center for Drug
and Alcohol Programs, Medical University of South Carolina, 67
President Street, Charleston, SC 29425, USA. bradyk@musc.edu
Anticonvulsant agents show promise in the treatment of the
acute symptoms of alcohol withdrawal and may also treat some symptoms
associated with the protracted abstinence syndrome. Impulsivity,
hostility and irritability are common characteristics of alcohol-dependent
individuals, and there is some evidence that anticonvulsant agents
decrease these traits in individuals with a number of different
psychiatric disorders. This pilot study is a 12-week, double-blind,
placebo-controlled trial of an anticonvulsant agent, divalproex
(DVPX), in alcohol-dependent individuals. Alcohol use (Timeline
Follow Back), impulsivity (Barratt Impulsivity Scale), irritability
and aggression (Buss-Durkee Hostility Index; and Anger, Irritability,
Aggression Scale) were measured at baseline and throughout the
12-week treatment period. Drinking decreased significantly in
both the placebo and the DVPX-treated groups. In the DVPX group,
a significantly smaller percentage of individuals relapsed to
heavy drinking, but there were no significant differences in other
alcohol-related outcomes. There were significantly greater decreases
in irritability in the DVPX-treated group and a trend towards
greater decreases on measures of lability and verbal assault.
There were no significant between-group differences on measures
of impulsivity. While DVPX did not have a robust effect on alcohol-related
outcomes, it did have modest impact on a measure of irritability.
This is consistent with the findings of other investigators exploring
the use of DVPX in schizophrenia, personality disorder and a number
of other psychiatric disorders.
-----
Paediatr Drugs. 2002;4(8):493-502.
Alcohol use disorders in adolescents: epidemiology,
diagnosis, psychosocial interventions, and pharmacological treatment.
Clark DB, Bukstein O, Cornelius J.
Department of Psychiatry, University of Pittsburgh Medical Center,
Pittsburgh, PA 15213, USA. clarkdb@msx.upmc.edu
Alcohol (ethanol) abuse and dependence are the most common
substance use disorders among adolescents. Binge drinking occurs
in up to one-third of adolescents, and alcohol use disorders occur
in about 6% of this age group. Adolescents with alcohol use disorders
also typically have problems with other substances and comorbid
mental disorders. Validated measures are available for the clinical
detection and diagnosis of adolescent alcohol use disorders and
related problems. Psychosocial interventions promoting abstinence
are the most common treatments for alcohol use disorders, with
empirical support particularly strong for family-based approaches.
Pharmacological interventions may diminish the effects of alcohol
withdrawal, prevent a return to alcohol consumption, or treat
comorbid mental disorders. In this population, pharmacological
interventions require further investigation and, where indicated,
are generally considered to be supplementary to psychosocial approaches.
-----
Alcohol Alcohol. 2002 Jul-Aug;37(4):375-82.
Does psychosocial treatment enhance the efficacy
of acamprosate in patients with alcohol problems?
De Wildt WA, Schippers GM, Van Den Brink W, Potgieter AS, Deckers
F, Bets D.
The Amsterdam Institute for Addiction Research, Amsterdam, The
Netherlands.
AIMS: Acamprosate in combination with psychosocial treatment
has been shown to be effective for the treatment of alcohol dependence.
The goal of the present study was to determine whether the addition
of psychosocial intervention to the medical prescription of acamprosate
contributes to treatment outcome. METHODS: Patients (n = 248)
meeting DSM-IV criteria for alcohol dependence or abuse were recruited
in 14 outpatient treatment centres and randomized into one of
three treatment conditions: acamprosate; acamprosate plus minimal
intervention aimed at motivational enhancement (3-weekly sessions
of 20 min); and acamprosate plus brief cognitive behavioural therapy
(7-weekly sessions of 60 min). Acamprosate was prescribed for
28 weeks, medically monitored by a physician on six occasions
lasting 10 min. Drinking behaviour, medication compliance and
psychological distress were assessed throughout the treatment
period. Follow-up assessment was undertaken 6 months after termination
of pharmacological treatment. RESULTS: Of 241 patients with intention
to treat (ITT), 114 (47.3%) remained in treatment for the full
28 weeks; 169 of the ITT population (70.1%) were seen for follow-up.
No statistically significant differences were found between treatment
groups for any of the drinking outcomes either at the end of the
28 weeks of treatment or at 6-month follow-up. There were no statistically
significant differences in medication compliance, drop-out rates,
or psychological distress. However, a significant interaction
effect was observed between treatment centre and treatment group,
indicating that brief interventions were differentially effective
in different treatment centres. CONCLUSIONS: A clear supplemental
value of minimal and brief psychosocial interventions to the prescription
of acamprosate was not demonstrated. The widely held belief that
pharmacotherapy for alcohol dependence should always be combined
with psychosocial intervention is debatable and merits further
research.
-----
Med J Aust. 2002 Jul 15;177(2):103-7.
New pharmacotherapies for alcohol dependence.
Graham R, Wodak AD, Whelan G.
St Vincent's Hospital, Sydney, NSW, Australia.
Two pharmacotherapies recently introduced in Australia, acamprosate
and naltrexone, provide a major advance in the treatment of severe
alcohol dependence, a common condition leading to a considerable
burden of illness and major costs to the community. Acamprosate
and naltrexone reduce alcohol intake, and increase the likelihood
and prolong the duration of abstinence (Level I evidence). Compared
with naltrexone, the benefits of acamprosate have been confirmed
in a larger number of studies involving larger numbers of patients
with longer durations of follow-up. Unlike naltrexone, acamprosate
appears to achieve a sustained benefit. There is no known interaction
effect between alcohol and acamprosate or naltrexone. Both drugs
are well tolerated, although naltrexone blocks the action of opioid
analgesics. Adjunctive psychosocial treatment with close follow-up
is required for acamprosate and recommended for naltrexone. As
yet, no studies have reported a reduction in mortality following
the use of any pharmacotherapy for alcohol dependence.
-----
Cochrane Database Syst Rev. 2002;(2):CD001867.
Opioid antagonists for alcohol dependence.
Srisurapanont M, Jarusuraisin N.
Department of Psychiatry, Chiang Mai University, P.O. Box 102,
Amphur Muang, Chiang Mai 50202, Thailand. msrisura@med.cmu.ac.th
BACKGROUND: The results from animal studies suggest that opioid
antagonists may prevent the reinforcing effects of alcohol consumption.
Based on the results of those animal studies, some opioid antagonists,
such as, naltrexone, nalmefene, have been studied for their benefits
in treating alcohol dependence. OBJECTIVES: To determine the effectiveness
of opioid antagonists in attenuating or preventing the recommencement
of alcohol consumption in patients with alcohol dependence in
comparison to placebo, other medications and psychosocial treatments.
In addition, discontinuation rate, death, patient satisfaction,
functioning, health-related quality of life and economic outcomes
were also evaluated. SEARCH STRATEGY: Electronic searches of Cochrane
Controlled Trials Register (Cochrane Library 2001, issue 4), MEDLINE
(1966 - October 2001), EMBASE (1980 - December 2001), and CINHAL
(1982 - December 2001) were undertaken. Du Pont Pharmaceutical
and Ivax Corporation were contacted for information regarding
unpublished trials. The reference lists of the obtained papers
were also examined. SELECTION CRITERIA: All relevant randomised
controlled trials (RCTs) and controlled clinical trials (CCTs)
were included. Participants were people with alcohol dependence.
Naltrexone (NTX), nalmefene (NMF) and other opioid antagonists
with/without other biological or psychosocial treatments were
examined. Four primary outcomes of interest were number of patients
who return to drinking, percentage or number of drinking days,
number of standard drinks of alcohol and amount of alcohol consumed.
A number of secondary outcomes were also considered. DATA COLLECTION
AND ANALYSIS: Two reviewers evaluated and extracted the data independently.
The dichotomous data were extracted on an intention-to-treat basis.
The Relative Risk with the 95% confidence interval was used to
assess the dichotomous data. Weighted (or Standardised) Mean Difference
with 95% confidence interval was used to assess the continuous
data. MAIN RESULTS: The review included 19 RCTs or CCTs presented
in 26 articles. In comparison to placebo, two of four short-term
primary outcomes were significantly in favour of NTX. Those were
number of patients who return to drinking (61% in NTX group vs
69% in placebo group) [RR (95% CI) = 0.88 (0.80 to 0.98), NNT
= 14] and percentage or number of drinking days [WMD (95% CI)
= -4.52 (-5.29 to -3.75)]. However, the short-term discontinuation
rates were high and not different between NTX and placebo groups
[RR (95% CI) = 0.96 (0.81 to 1.13)]. No medium-term outcomes of
NTX and placebo groups showed any significant difference after
the completion of NTX treatment for three to six months. However,
those who were regularly treated with NTX treatment in both short
and medium terms consumed smaller amounts of alcohol than placebo-treated
patients. Because of the small sample sizes, there were few significant
differences for other comparisons. REVIEWER'S CONCLUSIONS: NTX
at the dose of 50 mg/day is effective for alcohol dependence in
short-term treatment. The optimal duration of NTX treatment may
be longer than 3 months. The evidence so far may be too little
to support the superiority of NTX to acamprosate and the inferiority
of NTX to disulfiram. NTX treatment should be concurrently given
with a psychosocial intervention. Other patterns of NTX administration
should not be used at present, e.g., a dose of three times a week,
combined NTX with other biological treatments. NMF has no role
for the treatment of alcohol dependence in clinical practice.
Randomised, double-blind, placebo-controlled trials of NTX treatment
in patients with alcohol dependence are still needed. Some issues
should be concerned in further studies. Firstly, further trials
should be conducted in larger sample sizes and over longer periods
of time. Secondly, other than the outcomes relevant to alcohol
use, some important outcomes should also be measured, e.g., functioning,
health-related quality of life, economic cost. Thirdly, the comparisons
between NTX and other treatments for alcohol dependence, both
biological and psychosocial, should be investigated. Fourthly,
combined treatments of NTX and other biological treatments for
alcohol dependence may be in issue of interest. Lastly, high discontinuation
rate in both treatment and control groups should be concerned.
-----
Med J Aust. 2002 Jun 3;176(11):530-4.
Naltrexone in alcohol dependence: a randomised
controlled trial of effectiveness in a standard
clinical setting.
Latt NC, Jurd S, Houseman J, Wutzke SE.
Faculty of medicine, University of Sydney and Herbert Street Drug
and Alcohol Clinic, Royal North Shore Hospital, St Leonards, NSW
2065, Australia. nlatt@mail.usyd.edu.au
OBJECTIVES: To determine whether naltrexone is beneficial in
the treatment of alcohol dependence in the absence of obligatory
psychosocial intervention. DESIGN: Multicentre, randomised, double-blind,
placebo-controlled trial. SETTING: Hospital-based drug and alcohol
clinics, 18 March 1998 - 22 October 1999. PATIENTS: 107 patients
(mean age, 45 years) fulfilling Diagnostic and statistical manual
of mental disorders (4th edition) criteria for alcohol dependence.
INTERVENTIONS: Patients with alcohol dependence were randomly
allocated to naltrexone (50 mg/day) or placebo for 12 weeks. They
were medically assessed, reviewed and advised by one physician,
and encouraged to strive for abstinence and attend counselling
and/or Alcoholics Anonymous, but this was not obligatory. MAIN
OUTCOME MEASURES: Relapse rate; time to first relapse; side effects.
RESULTS: On an intention-to-treat basis, the Kaplan-Meier survival
curve showed a clear advantage in relapse rates for naltrexone
over placebo (log-rank test, chi(2)(1) = 4.15; P = 0.042). This
treatment effect was most marked in the first 6 weeks of the trial.
The median time to relapse was 90 days for naltrexone, compared
with 42 days for placebo. In absolute numbers, 19 of 56 patients
(33.9%) taking naltrexone relapsed, compared with 27 of 51 patients
(52.9%) taking placebo (P = 0.047). Naltrexone was well tolerated.
CONCLUSIONS: Unlike previous studies, we have shown that naltrexone
with adjunctive medical advice is effective in the treatment of
alcohol dependence irrespective of whether it is accompanied by
psychosocial interventions.
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